IndraLab
Statements
sparser
"As shown in xref , TA bound to IL-1β in a dose-dependent and saturable manner, and the equilibrium dissociation constant K D was 8.224 × 10 −7 M. Taken together, it can be inferred that TA is capable of binding to IL-1β to block IL-1β-induced bioactivity by inhibiting IL-1β-IL-1R1 interaction."
sparser
"Likewise, culture of stage 3 iNK cells in the continuous presence of a 100-fold molar excess of IL-1 receptor antagonist (IL-1RA), a naturally occurring specific competitive inhibitor of IL-1β binding to IL-1R1 ( xref ), completely abrogated the IL-1β-mediated expansion observed earlier ( xref )."
sparser
"Furthermore, CD117 + cells, which co-express CD161 and IL-22, and thus correspond to the IL-1R1 hi subpopulation of stage 3 iNK cells, reside in the lamina propria and parafollicular T cell-rich area of human tonsil, and co-localized with a cellular source of IL-1β found in CD11c hi cDCs, attesting to the physiologic relevance of the IL-1β-IL-1R1 interaction in vivo ."
sparser
"Additionally, the anti-inflammatory effect of BM-MSCs was confirmed in our patients by an increased level of the interleukin 1 receptor antagonist (IL-1Ra), a naturally-occurring cytokine that inhibits the binding of IL-1β to IL-1R. Muscle inflammation in DMD is primarily mediated by the IL-1β pathway, and the inhibition of its activity may potentially decrease inflammatory effects (the anti-inflammatory properties of IL-Ra were proved in the mdx mouse model through a functional improvement of the dystrophic muscle) [ xref ]."
reach
"During infection, mucosal injury and stress, the activation of IL-1beta can trigger local mucosal immune responses, by stimulating T cell proliferation, and direct neutrophils to injury or infection site through the combination of IL-1beta and IL-1R complexes, and further activate NF-kappaB and MAPK pathways, leading to the upregulation of other pro inflammatory cytokines and chemokines (such as IL-6, IL-8, and TNF)."
sparser
"RNA sequencing, quantitative real-time PCR, western blot, immunohistochemistry, RNAscope ISH, pharmacologic and genetic approaches were performed to examine the roles of spinal NLRP3 (The NOD-like receptor family, pyrin containing domain 3) inflammasome activation and IL-1β-IL1R1 signaling in chronic itch."
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"Fourth, Sirt6 deficiency-mediated aggravation of inflammation, senescence, TAA formation and survival was rescued by genetic inhibition (genetic knockout of Il1b) or pharmacological intervention in the IL-1β signaling pathway (inhibition of IL-1β binding to IL-1R), indicating that inhibition of IL-1β signaling contributes to SIRT6 function."
sparser
"Although the present study reports that IL-1β-direct targeting of TA showed anti-IL-1β activity by hindering the interaction between IL-1β and IL-1R1, further investigations are still needed to confirm whether TA can be applied as a therapeutic agent for other IL-1β-related diseases."
sparser
"These three pairs have been shown to work synergistically to induce pro-inflammatory cytokines in astrocytes. xref Predicted downstream target genes of IL1B-IL1R1 in astrocytes included C3 , the widely used marker of reactive astrocytes, as well as bZIP family TFs FOSL1 , XBP1 , and CEBPD ."
reach
"IL-1alpha and IL-1beta bind the same receptor, IL-1R1, and share similar proinflammatory properties mainly through the induction of cyclooxygenase type-2, type 2 phospholipase A, and inducible nitric oxide synthase, leading to recruitment of myeloid cells, including neutrophils, to sites of inflammation 16."
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"IL-1β binds to IL-1R in synoviocytes, which activates transcription factors through NF-κB and MAPK signaling pathways, regulates the inflammatory response, and leads synoviocytes to produce inflammatory mediators such as MMPs, COX-2, PGE2, NO, and other catabolic factors, accelerating cartilage degradation [23,24,25]."
sparser
"We have corrected the abbreviations and signs in the revised figure legend (Revised lines 562-565, 592, 603, and 611). “Binding of IL-1β and IL-1R1 without any single compound was used as a positive control (P.C.), and nonspecific binding of IL-1β and HRP-conjugated anti-human IgG secondary antibody without any single compound and IL-1R1 was used as a negative control (N.C.). ** p <0.01 compared to the positive control group.” and ““+” indicates treated and “-” indicates un-treated.”"
sparser
"Once secreted, Il-1β binds to Il1r1 and recruits Il1rap to form a functional receptor complex and then regulates gene transcription via the NF-κB pathway. xref Comparably, activation of the Wnt/β-catenin pathway regulates gene transcription via nuclear translocation of β-catenin, which interacts with TCF/LEF (T-cell factor/lymphoid enhancer factor) to form an active transcriptional complex. xref , xref , xref These two pathways can reciprocally influence each other’s activities both positively and negatively, with the specifics of these interactions being highly dependent on the cellular, developmental, and disease context. xref For example, activation of the NF-κB pathway can interfere with β-catenin activity by inhibiting its translocation to the nucleus. xref In addition, NF-κB signaling can also indirectly obstruct Wnt/β-catenin signaling by inducing the expression of genes that promote the proteasomal degradation of β-catenin. xref Similarly, binding of Il-1β to the Il1r1/Il1rap receptor complex can activate the mitogen-activated protein kinase (MAPK) signaling pathway, and MAPK, as well as related protein kinases, can modulate β-catenin stability. xref , xref , xref Thus, the inhibitory effects of Il-1β on Wnt/β-catenin signaling are an example of the complex interactions between inflammatory and developmental signaling pathways that regulate cellular processes in health and disease."
sparser
"The activation of IL-1β can also stimulate the local mucosal immune response and cause mucosal injury by stimulating T-cell proliferation and neutrophil entry to the site of injury or infection through the binding of IL-1β and IL-1R. xref , xref Serum IL-6 is another reliable indicator of AP severity that can predict both organ failure and SAP. xref The production of IL-6 can activate several different pathways in the adaptive immune system, thereby exacerbating inflammation and negatively affecting barrier function. xref Tan et al. xref also found that serum IL-6 levels in patients with AP were positively correlated with the abundance of Enterobacter and Enterococcus in the intestinal microbiota and negatively correlated with the abundance of XI groups of Bifidobacterium and Clostridium ."
sparser
"The reduction in epidermal hyperplasia observed in the Vamp3 Δmyel mice, when compared to the control mice in the CFA modeling, could align with the proposed involvement of IL-1β-IL-1R signaling in promoting inflammatory responses, especially in the context of epidermal hyperplasia."
sparser
"In summary, IL-1β binding to the IL-1R in SM cells, activates transcription factors via the NF-κB and MAPK signaling pathways to regulate inflammatory responses, resulting in the production of inflammatory mediators in SM cells, such as MMPs, COX-2, PGE2, NO and other catabolic factors, which may accelerate cartilage degeneration."
reach
"We used an IL-1β neutralizing antibody and an IL-1 receptor antagonist (IL-1RA) to block the interaction between IL-1β and IL-1R in the abovementioned treatment system and found that blocking the IL-1β/IL-1R interaction significantly suppressed α-SMA and COL1A1 expression in LX-2 cells (Fig. 5L-N)."
reach
"However, it is unclear whether TA shows the anti-IL-1β activity by blocking the interaction between IL-1β and IL-1R1.Therefore, in this study, we aimed to unveil the anti-IL-1β property of TA, which blocks the interaction between IL-1β and IL-1R1, and to determine the applicability of TA as an anti-IL-1β therapeutic agent using human OA chondrocytes and a rat OA model."
reach
"Although the present study reports that IL-1β-direct targeting of TA showed anti-IL-1β activity by hindering the interaction between IL-1β and IL-1R1, further investigations are still needed to confirm whether TA can be applied as a therapeutic agent for other IL-1β-related diseases."
reach
"Indeed studies with anakinra, a non glycosylated form of the endogenous antagonist of the IL-1 receptor, IL-1Ra, and rilonacept, which binds to IL-1beta with high affinity and thus blocks the binding of IL-1beta to its receptor, have demonstrated promising therapeutic activity in patients with CAPS [XREF_BIBR - XREF_BIBR]."
reach
"The interleukin 1 receptor (IL1-R), which binds both IL1a and IL1b, two important inflammatory molecules associated with depression and other psychiatric disorders (Carvalho et al., 2014; Slavich and Irwin, 2014), was upregulated in both Balb/c and C57Bl6 mice at both time points."
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"To investigate whether the effects of HFD on HSCs could be counteracted by interfering with the interaction of IL-1β and IL-1r1 and reducing the activation of p38/MAPK signaling, the human IL-1β receptor antagonist anakinra was administered for a duration of 14 days during the development of obesity in mice [28] (Fig. 6A)."
reach
"IL-1alpha and IL-1beta bind to IL-1R1 and use IL-1RAcP as a common coreceptor and then recruit intracellular signaling molecules, including myeloid differentiation factor 88, IL-1R-associated kinase, and TNF receptor associated factor 6 (TRAF6) to activate nuclear factor-kappaB, as well as extracellular signal regulated kinase 1/2, c-Jun N-terminal kinase, and p38 MAPK 42."
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"Previously, we have shown that ex vivo sarcoidosis AMs exhibit elevated levels of pro-IL-1β and IL-1 receptor antagonist (IL-1RA).28 29 30 IL-1 RA is considered as a decoy receptor for IL-1β and thought that IL-1RA competitively binds to IL-1β and forms a nonsignaling complex that acts as a molecular trap by inhibiting IL-1beta activity on cells.38 Thus, we explored the effect of exogeneous MIF on pro-IL1β and IL1β in cultured sarcoidosis AMs."
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"Elevated IL-1RA has been reported in human autoimmune/inflammatory diseases, including rheumatoid arthritis and sarcoidosis.30 65 Although it is shown that IL-1RA acts as a decoy receptor and binds in vitro to IL-1β,38 66 the mechanism by which it is upregulated is not fully elucidated."
sparser
"IL-1β binds to its receptor IL-1R and recruits myeloid differentiation primary response protein MyD88 and IL-1R–associated kinase 4 (Irak4) to phosphorylate Irak1, enabling transient recruitment of TNF receptor–associated factor 6, dissociation of Irak1 from the receptor, and activation of Tak1 ( xref )."
reach
"Between T-cells and neutrophils 459 specific interactions involved CCR1 and CCL3 or CCL3L1 (pro inflammation), CD2 and CD58 (co460 stimulatory and immunogenic pathway) and CD94 : NKG2E and HLA-F (anti-viral immune-surveillance), 461 whereas between epithelial cells and neutrophils, IL1R and IL1A or IL1B or IL1R interactions were most 462 pronounced (which can facilitate productive neutrophil immunity in an immune463 controlled and immunogenic context) 28,33,34."
| DOI
sparser
"Moreover, IL-1β binds to IL-1R1 on the surface of intestinal epithelial cells and activates pro-inflammatory pathways mediated like MAPK/AP-1 or NF-κB that promote cell proliferation and survival, angiogenesis, invasion, and metastasis, ultimately leading to the development of CRC ( xref )."
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"In contrast, the scrambled peptide (SC) did not affect the IL-1β-His and IL1R1 interaction (Lane 4), as evidenced by IL1R1 levels, which were similar to the control.These results demonstrate that LN can competitively inhibit the binding of IL-1β to IL1R1, likely by directly interacting with IL-1β and preventing its engagement with the receptor."
| PMC
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"We noted that the expression of IL-1β receptor, IL1R1 and selectin binding protein, P-selectin glycoprotein ligand 1 (PSGL-1) was markedly decreased in AIL neutrophils as compared with normal human neutrophils (Figure 7D), which further confirmed the critical roles of IL-1β and selectins in neutrophil-mediated apoptotic clearance."
reach
"The IL-1 pathway is triggered when the ligands IL-1alpha and IL-1 beta (IL-1beta) bind to IL-1 receptor type I (IL-1R1) that forms a complex with the IL-1 receptor accessory protein (IL-1RAcP) and then recruits myeloid differentiation primary response gene 88 (MyD88), IL-1 receptor associated kinases (IRAKs), and TRAF6 [XREF_BIBR]."
reach
"The increase in IL-1beta levels after one to three hours and in TNF-alpha levels after prolonged incubation with A. actinomycetemcomitans infected macrophages possibly indicated that the binding of IL-1beta to its receptor IL-1R1 led to a cascade of downstream events, eventually resulting in the expression of TNF-alpha."
reach
"Another opportunity to block neutrophil hyperactivation is acting on IL-1beta and IL-1R interaction; anakinra (IL-1R inhibitor) is currently under clinical investigation showing promising preliminary results, whereas canakinumab (IL-1beta inhibitor) failed to ameliorate the outcome of severe COVID-19 patients (https://www.novartis.com/news/media-releases/novartis-provides-update-can-covid-trial-hospitalized-patients-covid-19-pneumonia-and-cytokine-release-syndrome-crs)."
sparser
"Myeloid Differentiation Primary Response 88 (Myd88) is a significant constituent of the signalling cascade downstream of IL-1β-IL-1R interaction, which ultimately converges with the canonical NF-κB signalling pathway leading to the further amplification of the inflammatory mediator production in RA ( xref ; xref )."
sparser
"Binding of IL-1β to endothelial IL-1R1 activates endothelial cells and triggers the up-regulation of cell adhesion molecules such as endothelial cell selectin (E-selectin) and intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory cytokines such as IL-6 and TNF, and chemokines such as CXCL1, CXCL2, CXCL8, CX 3 CL1 and CXCL12 ( xref , xref - xref )."
sparser
"Clearly, these conflicting studies around IL-1β indicate a need for more research dedicated to understanding the key cellular players and cellular signaling events involved in IL-1β-IL-1R signal-mediated atherosclerotic calcification both in the presence and absence of statin therapy, as overlapping pathways albeit with some likely variations analogous to the changes we identified with regard to ROS may be involved."
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"Meanwhile, IL-1β can also directly binds to IL-1R on tumor cells and activates the MEK/ERK pathway through the IKKβ/Tpl2 cascade, inducing the expression of mesenchymal genes and enhancing cell migration and invasion capabilities.This dual-pathway synergistic mechanism originated from IL-1β secreted by neutrophils under the influence of neuroendocrine exosomes drives epithelial cells to retain partial epithelial markers through incomplete E-cadherin loss while simultaneously gaining mesenchymal characteristics via vimentin upregulation, thereby establishing a hybrid epithelial-mesenchymal phenotype."
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"IL-1β binds to its receptor IL-1R and recruits myeloid differentiation primary response protein MyD88 and IL-1R–associated kinase 4 (Irak4) to phosphorylate Irak1, enabling transient recruitment of TNF receptor–associated factor 6, dissociation of Irak1 from the receptor, and activation of Tak1 (49)."
reach
"It is known that TLR and the interleukin-1 receptor (IL-1R) superfamily share a conserved cytoplasmic domain and that the binding of IL-1beta to IL-1R induces activation of NF-kappaB and mitogen activated protein kinases (MAPKs), including extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen activated protein kinase (p38), through the interaction between the TIR domain and MyD88 XREF_BIBR, XREF_BIBR."
sparser
"IL-1β interacts with IL-1R and activates NF-κB to promote a wide range of biological effects capable of inducing morphological and phenotypic transdifferentiation of tubular epithelial cells into myofibroblast-like cells (Gasse et al. xref ; Stewart and Marsden xref ; Vesey et al. xref )."
reach
"Moreover, IL-1β binds to IL-1R1 on the surface of intestinal epithelial cells and activates pro-inflammatory pathways mediated like MAPK/AP-1 or NF-κB that promote cell proliferation and survival, angiogenesis, invasion, and metastasis, ultimately leading to the development of CRC (69)."
sparser
"In our analysis TAMs were the exclusive source of IL1B. Moreover, IL1B was identified as a key driver of cancer hallmarks, and its average ligand–receptor pair (IL1B–IL1R1) expression significantly correlated with single-sample enrichment scores of several cancer hallmarks in bulk MES data."
reach
"XREF_BIBR The effects of IL-1 are negatively regulated by 2 endogenous inhibitors, namely IL-1 receptor 2 (IL-1R2), which is related to the IL-1R1 and lacks a cytoplasmic domain, and IL-1 receptor antagonist IL-1Ra, which mimics the binding of IL-1beta to IL-1R1 but fails to recruit the IL-1RAcP, preventing downstream signaling."
sparser
"The binding of IL-1β to IL1R1 initiates a cascade of conformational changes in the intracellular proteins, beginning with the recruitment of IL1RAP and further signalling via the adaptor protein MYD88 to the kinases interleukin 1 receptor-associated kinases 2 and 4 (IRAK-2, 4) and the oligomerisation of tumour necrosis factor-associated factor (TRAF) 6."
sparser
"Once secreted, Il-1β binds to Il1r1 and recruits Il1rap to form a functional receptor complex and then regulates gene transcription via the NF-κB pathway. xref Comparably, activation of the Wnt/β-catenin pathway regulates gene transcription via nuclear translocation of β-catenin, which interacts with TCF/LEF to form an active transcriptional complex. xref – xref These two pathways can reciprocally influence each other’s activities both positively and negatively, with the specifics of these interactions being highly dependent on the cellular, developmental, and disease context. xref For example, activation of the NF-κB pathway can interfere with β-catenin activity by inhibiting its translocation to the nucleus. xref In addition, NF-κB signaling can also indirectly obstruct Wnt/β-catenin signaling by inducing the expression of genes that promote the proteasomal degradation of β-catenin. xref Similarly, binding of Il-1β to the Il1r1/Il1rap receptor complex can activate the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, and MAPK, as well as related protein kinases, can modulate β-catenin stability. xref – xref Thus, the inhibitory effects of Il-1β on Wnt/β-catenin signaling are an example of the complex interactions between inflammatory and developmental signaling pathways that regulate cellular processes in health and disease."
sparser
"IL-1β binds to IL-1R in synoviocytes, which activates transcription factors through NF-κB and MAPK signaling pathways, regulates the inflammatory response, and leads synoviocytes to produce inflammatory mediators such as MMPs, COX-2, PGE2, NO, and other catabolic factors, accelerating cartilage degradation [ xref , xref , xref ]."
sparser
"Ras activates MAPK and PI3K, and then triggers the transcription factor cMyc, directly inducing considerable expression of glycolytic genes, such as GLUT1 , HK2 , PFK , enolase, and LDHA . xref PI3K is activated by ligand binding to receptor tyrosine kinase via Akt, and then stimulate cMyc and HIF1α, in order to regulate GLUT1 and several glycolysis-related enzymes, eg, HK2, PFK, aldolase A, and LDHA. xref One study found that IL-1β could combine IL1R1 and activate NFκB, JNK, ERK1/2, and the p38-signal pathway. xref Dang et al discovered that the IL-1β–IL-1R1 pathway upregulated HOXC10 via the JNK–cJun pathway, affecting metastasis of liver cancer."
reach
"Previous studies reported that IL1beta and TNFalpha exert toxic effects by binding to their cognate receptors, IL1-R1 and TNFR1, respectively, triggering downstream signaling pathways that activate transcription factors, such as NFkappaB or AP1 which in turn lead to the production of NO and ROS."
sparser
"Interestingly, a structural complex of the IL-1R1-ECD with a small antagonist peptide is available (PDB entry 1G0Y), showing a 170° rotation of D3 relative to a reference D3 in the IL-1R1:IL-1β complex (PDB entry 1ITB), and thus exposing an unexpected binding mode for the peptide [ xref ]."
reach
"The IL-1 pathway is triggered when the ligands IL-1α and IL-1 beta (IL-1β) bind to the IL-1 receptor type 1 (IL-1R1) leading to the recruitment of the co-adaptor protein MyD88, IL-1 receptor-associated kinases (IRAKs) and TRAF6, which are important for prompting the expression of target genes involved in immune response [23]."
reach
"The IL-1 pathway is triggered when the ligands IL-1α and IL-1 beta (IL-1β) bind to the IL-1 receptor type 1 (IL-1R1) leading to the recruitment of the co-adaptor protein MyD88, IL-1 receptor-associated kinases (IRAKs) and TRAF6, which are important for prompting the expression of target genes involved in immune response [23]."
sparser
"In this way, various pro-inflammatory events, initiated by IL-1β:IL-1R or TNF:TNFR binding, including the synthesis and releases of T cell-attracting chemokines, enhanced influx of leucocytes and post-translational modifications of ion channels in inflamed eyes of DED patients, are inhibited by MSC-derived IL-1Ra and sTNFR [ xref , xref ]."
sparser
"As the
ligand-recognition receptor, IL-1R1 binds IL-1β directly leading to activation of
NF-kB and induction of a range of downstream proteins related to inflammatory response. xref Although IL-1RAP cannot bind IL-1β directly, it is essential for the
formation of an activated membrane receptor complex, which recruit intracellular
adaptor proteins and kinases, including MyD88, IL-1 receptor-associated kinase 1
(IRAK1) and IRAK4. xref CEBPB (also named NF for IL-6, NF-IL6) is a transcription factor activated by
LPS or IL-17, and itself regulates numerous genes involved in inflammation,
including IL-6 and IL-23R. xref , xref CRP is a major acute-phase reactant and marker of inflammation, which is
produced by the liver. xref Some researchers have reported an association between lower CRP levels and
increased dietary intake of EPA and DHA. xref , xref IL-18 is necessary for the development of Cutibacterium
acnes /LPS-induced liver injuries. xref Blockade of IL-18 can protect against the liver damages. xref Kupffer cells secrete IL-18 in a manner dependent on TRIF and the NLRP3
inflammasome after stimulation with LPS. xref IL-18BP, a specific antagonist of IL-18, binds to IL-18 and functions as a
competitive inhibitor of receptor binding of IL-18. xref In our study, FO increased the expression of IL-18BP after LPS challenge,
which might prevent IL-18 activation and protect against the liver injury."
sparser
"It is known that TLR and the interleukin-1 receptor (IL-1R) superfamily share a conserved cytoplasmic domain and that the binding of IL-1β to IL-1R induces activation of NF-κB and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38), through the interaction between the TIR domain and MyD88 xref , xref ."
sparser
"Therefore, the expression of IL1β in cells and tissues that encounter eLNPs presents the challenge of how the initial TLR-dependent expression of IL1β can be distinguished from its subsequent expression that is self-potentiated by IL-1β binding to IL-1R. Furthermore, at the protein level, post-translational modifications are necessary to activate the precursor of IL-1β, pro-IL-1β, and release the mature, biologically active form of IL-1β."
sparser
"α-TRPS Inhibitors BVDV Inhibitors Wee1 Inhibitors TLR2 Antagonists C-YesK Inhibitors PRMT5 Inhibitors DAAO Inhibitors Top2 Inhibitors BioA Inhibitors PDF Inhibitors TLR1/2 Agonists PRMT5 Inhibitors FXR Antagonists MELK Inhibitors MMP-2 Inhibitors CB1 Antagonists Calpain-1 Inhibitors VEGFR-2 Inhibitors PARG Inhibitors CDK4/6 Inhibitors Dual A2aAR/MAO-B Inhibitors PKM2 Inhibitors JAK2 Inhibitors AKA Inhibitors
6,000,000 1,000,000 212,770 5,744,976 2,200,000 207,345 2,000 287,000 260,071 1,671 10,519,614 1,671,908 4,000
53,290 278,037 36,503 500,000 31,000 3,167 5,400,000 30,000 260,000 230,000
IL-1β–IL-1R1 Regulators WTA Inhibitors GLUT3 Inhibitors Dual AChE/PARP-1 Inhibitors H-Ras Inhibitors
1,500,000 88,700 500,000 863 16,208
7 (1) 19 (5) 19 (1) 13 (4) 25 (4) 120 (5) 16 (5) 37 (14) 78 (7) 15 (3) 14 (1) 158 (4) 30 (6) 25 (2) 20 (3) 18 (7) 10 (3) 11 (1) 68 (2) 9 (1) 24 (4) 65 (5) 9 (1)
17
GOLD ICM DockScan ICM GOLD GOLD Glide Glide Glide GOLD AutoDock FlexX Glide Glide Glide
AutoDock Vina Glide Glide ChemBio 3D Glide idock DOCK UCSF DOCK LeadIT AutoDock
60 (1) 39 (3) 13 (2) 10 (3) 30 (3)
Glide Glide Glide AutoDock Vina Glide
Aldrich eMolecules ZINC, MayBridge, In-house set Specs ZINC, Known actives ZINC, Enamine Specs In-house set Specs NCI ZINC ZINC Chemdiv, Specs, TargetMol NPD
ChEMBL ZINC12 Aldrich- MSD (2016) ChemBridge AZ ZINC ZINC ZINC, Specs NCI ChemDiv, InterBioScreen, Asine, Specs, Enamine ChemBridge Asinex, LifeChemicals, Selleck, Enamine, ChemDiv Listed Belowg PubChem MayBridge
[174] [102] [103] [104] [105] [106] [74] [107] [108] [109] [110] [111] [112] [113] [114] [115] [169] [116] [117] [167] [118] [119] [120] [121]
[170] [122] [123] [124] [125] [126]
a1NMR post-docking evaluation."
reach
"Both PA401 and HuMax-IL8 have not been evaluated in patients with COPD.The IL-1 family consists of two related polypeptides, IL-1α and IL-1β that bind to the same primary receptor IL-1R1, which is expressed by almost all cell types, and can recruit and/or activate a variety of immune cells and immunocompetent cells, such as macrophages, endothelial cells, neutrophils, and epithelial cells."
sparser
"Alternatively, IL-1β–IL-1R interactions could be targeted therapeutically, as we described with the use of anakinra (IL-1R inhibitor) and neutralizing antibodies against IL-1β, to serve the dual purpose of not only preserving endothelial integrity ( xref ), but also attenuating the recruitment of inflammatory splenic monocytes."
reach
"In response to IL1beta binding to IL1R1, a complex sequence of combinatorial phosphorylation and ubiquitination events results in activation of nuclear factor kappaB (NF-kappaB) signaling and the JNK and p38 mitogen activated protein kinase pathways, which cooperatively induce the expression of canonical IL1beta target genes (such as IL-6, CXCL8, CCL2, COX-2, IkappaBalpha, IL1alpha, IL1beta, MKP-1) via transcriptional and post-translational modifications."
sparser
"The increase in IL-1β levels after one to three hours and in TNF-α levels after prolonged incubation with A. actinomycetemcomitans- infected macrophages possibly indicated that the binding of IL-1β to its receptor IL-1R1 led to a cascade of downstream events, eventually resulting in the expression of TNF-α."
sparser
"IL-1β is produced by myeloid cells after activation of Toll-like receptors or retinoic acid-inducible gene-like receptors. xref , xref , xref It is synthesized as a precursor protein, pro-IL-1β, that may be cleaved into mature IL-1β by caspase-1 within an activated inflammasome. xref Mature IL-1β exerts pro-inflammatory effects by binding to the IL-1 receptor type 1 (IL-1R1) that allows its interaction with the co-receptor IL-1R3 with subsequent transcription of inflammatory target genes. xref The downstream effects of IL-1β are modulated by the IL-1 receptor antagonist (IL-1RA), which is an endogenous antagonist to IL-1β that competitively binds IL-1R1 and prevents downstream signaling. xref "
reach
"Furthermore, our results indicated that the activation of the Nrf2 pathway upon IL-1β stimulation is further enhanced by tamarixetin treatment, thereby boosting the cellular antioxidative system.When IL-1β binds to IL-1R, the myeloid differentiation primary response 88-dependent pathway can activate both the MAPK and NF-κB signaling pathways, which can exacerbate inflammation and dysfunction of chondrocytes [54]."
reach
"Although aged skin did show a greater induction of IL1R2 gene expression in response to both IL-1beta and TNF-alpha, suggesting that under inflammatory conditions IL-1beta signalling may be further suppressed due to greater availability of the IL-1R2 decoy receptor, which reduces IL-1beta binding to IL-1R1 and sequesters IL-1RAP.34 In aged skin the addition of recombinant IL-1beta protein may provide a large enough signal to induce IL1B gene expression in the target cell, and/or may bypass the need for de novo IL-1beta synthesis."
reach
"Because corticosteroids are well-known to induce IL-1 Receptor Antagonist (IL-1RA) transcription (Levine et al., 1996), which binds to both IL-1α and IL-1β, we believed that the administration of corticosteroids was able to reduce IL-1α release, which we demonstrated to be responsible for TGF-β release during the exacerbation phase of COPD (Colarusso et al., 2019)."
sparser
"After binding to the receptor of advanced glycation end products (RAGE), UA-induced HMGB1 activates the NF-κB signaling pathway and promotes the production of the inflammatory cytokines IL-6 and TNF-α, leading to oxidative stress and inflammatory responses. xref In addition, a recent report showed that the microbiota can induce the production of IL-1β and that stimulation of IL-1β-IL-1R signaling is essential to promote the differentiation of Th17 cell. xref Studies have shown that the differentiation of cytokines related to IL-17 signaling pathway is related to the colonization of intestinal flora and may participate in intestinal immune homeostasis. xref "
reach
"IL-1α or IL-1β forms a complex with IL1R1 and IL1RAP at the cell membrane, mediating the acute phase of the proinflammatory process during infection or tissue damage, which initiates the IL-1 signaling pathway and leads to recruitment of adaptor proteins like myeloid differentiation primary response gene 88 (MYD88), Toll-interacting protein (TOLLIP), and IL-1 receptor-associated kinase 4 (IRAK4)."
reach
"The binding of IL-1β to IL1R1 initiates a cascade of conformational changes in the intracellular proteins, beginning with the recruitment of IL1RAP and further signalling via the adaptor protein MYD88 to the kinases interleukin 1 receptor-associated kinases 2 and 4 (IRAK-2, 4) and the oligomerisation of tumour necrosis factor-associated factor (TRAF) 6."
reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR Binding of IL-1alpha or IL-1beta to IL1R1 leads to the activation of a series of protein kinases that subsequently trigger an increase in the expression of numerous pro inflammatory genes, XREF_BIBR, XREF_BIBR and in some cells triggers apoptosis, XREF_BIBR, XREF_BIBR likely depending on the local concentration of IL-1alpha and IL-1beta."
reach
"IL-1β then binds its cognate IL-1 receptor 1 (IL-1R1) and recruits IL-1R1 accessory protein (IL-1RAcP) to activate the myeloid differentiation primary response 88/p38 mitogen-activated protein kinase (MyD88/p38 MAPK) pathway and trigger an inflammatory response (Davis et al., 2006; Nemeth and Quan, 2021)."
sparser
"IL-1β signaling can be blocked by the decoy receptor IL1R2 either by preventing the interaction of IL-1β with IL1R1 through competitive binding [ xref , xref ] or by decreasing the concentration of IL1RAP, which is an essential member of the signaling complex, by forming a non-signaling complex with IL-1β and IL1R2 [ xref , xref ] ( xref and xref )."
reach
"Likewise, culture of stage 3 iNK cells in the continuous presence of a 100-fold molar excess of IL-1 receptor antagonist (IL-1RA), a naturally occurring specific competitive inhibitor of IL-1beta binding to IL-1R1, completely abrogated the IL-1beta-mediated expansion observed earlier (XREF_FIG)."
sparser
"Anakinra is a recombinant form of the IL-1 receptor antagonist, which, similarly to its endogenous analog, is able to competitively inhibit the binding of IL-1β to its receptor IL1R. This drug has been used successfully in numerous autoimmune and auto-inflammatory conditions, including cytokine release syndrome (CRS) secondary to CAR-T cell therapy and HLH [ xref , xref , xref ]."
reach
"IL-1α, and IL-1β bind IL-1R1, IL-33 binds ST2, IL-18 and IL-37 bind IL-18Ra, IL-37 also binds a decoy receptor IL-1R8 through which it mediates some anti-inflammatory activity, and the IL-36 cytokines all bind IL-36R.All IL-1 family cytokines are expressed, with some variation, within the skin."
sparser
"This mode of activation is somewhat similar to that of mammalian IL-1R. The expression of pro-IL-1β is induced by PAMPs and pro-IL-1β is proteolytically cleaved by Caspase-1 or Caspase-4/11 leading to the release of mature IL-1β that can bind IL-1R. However, there is no evidence that mammalian TLRs are activated by PAMPs through protein ligands analogeous to Drosophila spatzel."
sparser
"Typically, toll-like receptor stimulation in response to microbial infection results in binding of IL-1β to the IL-1R1 and leads to activation of: nuclear factor κ B (NFκB), p38 mitogen-activated protein kinase (p38 MAPK) as well as other kinases, and the hypothalamic pituitary-adrenal (HPA) axis."
sparser
"Fourth, Sirt6 deficiency-mediated aggravation of inflammation, senescence, TAA formation and survival was rescued by genetic inhibition (genetic knockout of Il1b ) or pharmacological intervention in the IL-1β signaling pathway (inhibition of IL-1β binding to IL-1R), indicating that inhibition of IL-1β signaling contributes to SIRT6 function."
sparser
"It is also relevant to note that the rapid translocation of RAGE to the cell surface during inflammatory activation is partly under NF-kB control [ xref , xref ] which is signalled via both the TLR4 and IL-1β-IL-1R pathways to MyD88, adding a further amplification pathway to that of RAGE-mediated uptake with further inflammasome release and pyroptosis."
| PMC
reach
"These pro-inflammatory cytokines, IL-6 and IL-8, can be produced by IL-1β stimulation in human GFs and PDLs.IL-1β is an important target in the regulation of inflammation-related diseases; there have been numerous studies regarding small molecules that affect IL-1 signaling by hindering the interactions between IL-1β and IL-1R [2,17,32,33,34]."
reach
"Furthermore, we revealed that IL-1β, released by NLRP3 inflammasome activation, could directly bind to IL-1R-1 in lymphatic endothelial cells (LECs), and enhance tube formation capacity of LECs, indicating the potential role of NLRP3 inflammasome in promoting lymphangiogenesis and metastasis in OSCC."
sparser
"We have previously demonstrated that adoptive transfer of purified microglia from hTau- Cx3cr1 – / – mice that exhibit a highly inflammatory phenotype, into the brains of non-transgenic recipient mice was sufficient to induce tau pathology in a manner dependent upon IL-1β-IL-1R axis ( xref )."
sparser
"We used an IL-1β neutralizing antibody and an IL-1 receptor antagonist (IL-1RA) to block the interaction between IL-1β and IL-1R in the abovementioned treatment system and found that blocking the IL-1β/IL-1R interaction significantly suppressed α-SMA and COL1A1 expression in LX-2 cells (Fig. xref L-N)."
reach
"Binding of IL-1beta to IL-1R elicits transduction signaling that activates nuclear factor kappa B (NF-kB) and mitogen activated protein kinase (MAPK) pathways to promote production of itself as well as induce expression of other proinflammatory cytokines like TNFalpha and IL-6 [XREF_BIBR]."
reach
"The produced IL-1β can bind to its receptor IL1R1 and recruit the adaptor protein MyD88, which leads to the activation of several signaling pathways including NFκB- and MAPK-mediated signaling events, that regulate inflammatory gene expression and production of cytokines like IL-6, TNF-α, and IL-1α (45)."
sparser
"Binding of IL-1β to IL-1R1 results in myeloid differentiation primary response protein 88 (MyD88)-dependent and MyD88-independent pathway activation, including induction of c-Jun N-terminal kinase (JNK), p38 MAPK, and NFκB, thus modulating proliferation, cell survival, apoptosis, and immune responses [ xref , xref ]."
| PMC
reach
"Attenuation but not complete elimination of IL-1beta induced FGF2 expression and enhanced cell migration by sulfasalazine, a NF-kappaB inhibitor, and SB203580, an AP-1 inhibitor, showed that IL-1beta binding to IL-1R1 led to a parallel activation of AP-1 and NF-kappaB in human CEC."
reach
"The great abundance of IL1B, IL1R1, and IL1RAP and low abundance of IL1RN at the maternal-conceptus interface during the implantation period suggest that endometrial IL1R1 and IL1RAP expression is regulated by factors of conceptus origin, such as estrogen and IL1B, and that IL1B secreted by the conceptus plays a critical role in implantation by binding to IL1R1 and IL1RAP on the uterine endometrium."
sparser
"The produced IL-1β can bind to its receptor IL1R1 and recruit the adaptor protein MyD88, which leads to the activation of several signaling pathways including NFκB- and MAPK-mediated signaling events, that regulate inflammatory gene expression and production of cytokines like IL-6, TNF-α, and IL-1α ( xref )."
reach
"Regardless of the intracellular signaling mechanisms, the primary outcome of inflammasome activation is the activation of caspase-1 and cleavage of pro-IL-1beta to IL-1beta, which binds to the IL-1R, and stimulates hepatic recruitment of IL-1R expressing cells, resulting in inflammation."
sparser
"Binding of IL-1β to IL-1R1 could directly stimulate myelopoiesis in a cell-intrinsic fashion, or alternatively induce a signaling cascade leading to the production of proliferative cytokines (e.g. G-CSF, M-CSF), which, in turn, act on other hematopoietic or non-hematopoietic cells (e.g., endothelial cells) in a cell-extrinsic fashion."
sparser
"These data indicated that DS may inhibit the activation of NLRP3 inflammasome signaling via inducing mitophagy in CCI-induced neuropathic mice, thereby reducing the pain signal conduction caused by the binding of IL-1β to IL-1R on the spinal dorsal horn neurons, therefore raising the pain threshold."
sparser
"Binding of IL-1β to IL-1R elicits transduction signaling that activates nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) pathways to promote production of itself as well as induce expression of other proinflammatory cytokines like TNFα and IL-6 [ xref ]."
reach
"Therefore, one can hypothesize that the activity of the SNPs in this haplotype, or an unmeasured SNP (s) in linkage disequilibrium, decreases IL1R2 expression, which would increase the amount of pro inflammatory IL1-beta bound to IL1R1 and result in higher levels of trait and state anxiety."
reach
"The attendant cytokine recognition and assembly mechanisms of IL-1 receptors were only partly disclosed by the structure of the IL-1beta and IL-1R1 heterodimer complex, which further left open the inviting prospect of a face-to-face (or pseudosymmetric) docking of the unseen IL-1RAcP co-receptor chain."
reach
"Both IL-1alpha and IL-1beta interact with the IL-1 receptor 1 (IL-1R1) and recruit the IL-1 receptor accessory protein (IL-1R3, formerly IL-1RAcP) to induce a downstream signal via several inflammatory kinases, such as Myd88, ERK, JNK and NFkappaB, leading to transcription of inflammatory, catabolic genes [XREF_BIBR - XREF_BIBR]."
reach
"As building block components of the respective complexes, we took the crystal structure of the IL-1beta and IL-1R1 complex and the calculated model of the IL-33 and ST2 complex, together with the common subunit, a homology model of the co-receptor (also built on the IL-1R1 template)."
sparser
"In addition, the anti-IL-1R1 antibody significantly decreased the number of infiltrated Ly6G + neutrophils in both Atg7 fl/fl and Atg7 fl/fl ;LysM-Cre mice (Fig. xref b), supporting the role of IL-1β–IL-1R signalling in driving neutrophilic inflammation during psoriatic skin inflammation, particularly in the context of autophagy deficiency."
sparser
"Similarly, we observed a reciprocal dysregulation of autophagy-related genes ( ATG7 vs. ATG14 and SQSTM1 ) and overexpression of genes related to inflammasomes ( NLRP3 , CASP1 , and PYCARD ) and IL-1β–IL-1R1 signalling ( IL1B , IL1R1 , MyD88 , IRAK1 , IRAK2 , and IRAK4 ), which correlated with the Th17 pathway (Supple."
reach
"Casadio et al. showed that an antibody directed against residues in the beta6-beta7 turn and strand beta7 of IL-1beta (residues 73-81) did not inhibit the biological effect of IL-1beta in cell based assays, thus disfavoring their computationally derived ' front ' model for the interaction of IL-1RAcP with the IL-1beta and IL-1R1 complex."
reach
"Several mechanisms exist for negatively regulating IL-1RI signalling, including IL-1RII that binds both IL-1alpha and IL-1beta and acts as a decoy receptor, and IL-1Ra that serves as an endogenous competitive inhibitor of IL-1alpha and IL-1beta by binding but not activating IL-1RI."
reach
"IL-1β activates the IL-1R1-TLR4 signaling pathway by binding to IL-1R1, which can decrease the expression of GABA receptor and increase the expression of N-methyl-D-aspartate (NMDA) receptor in neurons and glial cells (Dheer et al., 2018; Cramer et al., 2019; Sanz and Garcia-Gimeno, 2020; Semple et al., 2020)."
reach
"In mice, microglia activated by CS recruit monocytes that express high levels of interleukin-1β (IL-1β) that binds to interleukin-1 receptor type I-positive (IL-1R ) neurovascular endothelial cells, allowing monocytes to cross the blood-brain barrier (BBB) into the CNS and spread inflammatory signals."
reach
"While IL-1R1 binds IL-1α, IL-1β, and IL-1R antagonist (IL-1Ra) with approximately same high affinity (K
=10 M), IL-1R2 demonstrates the strongest affinity for IL-1β at 2.2×10 M. Conversely, its affinity for IL-1Ra and IL-1α is reduced by 100 and 1,000 times, respectively (K
=1.6×10 M and 1.4×10 M, respectively), compared to IL-1β (29)."
sparser
"Therefore, it is possible that various pro-inflammatory events initiated by IL-1β:IL-1R or TNF:TNFR binding, including the synthesis of immune cell-attracting chemokines followed by enhanced influx of circulating leucocytes in inflamed lacrimal and salivary glands of patients with pSS, might be inhibited by MSC-derived IL-1Ra and sTNFR [ xref , xref ]."
sparser
"The interleukin (IL)-1 superfamily includes 7 agonist proteins (including IL-1α and IL-1β), 3 receptor antagonists (including IL-1Ra) and the anti-inflammatory cytokine IL-37. xref IL-1α and IL-1β are distinct pro-inflammatory cytokines produced by multiple cell types, e.g., monocytes, macrophages, and neutrophils, as well as by cells in joint tissues e.g., synovial fibroblasts, chondrocytes and osteoclasts. xref They exert a wide range of biological and physiological effects throughout the body, including fever following stimulation in the central nervous system, innate resistance to infection, xref prostaglandin synthesis, xref T- and B-lymphocyte activation, IL-2 production, expression of cytokines, chemokines, nitric oxide synthetase, and matrix metalloproteinases (MMPs). xref IL-1α and IL-1β bind to the same receptor, namely the IL-1 receptor type I (IL-1R1) complexed to the IL-1 receptor accessory protein (IL-1RAcP) and induce similar physiological effects, including neutrophilia, fibroblast proliferation, cytotoxicity for certain cells, induction of collagenases, and increased production of colony stimulating factors and collagen. xref The effects of IL-1 are negatively regulated by 2 endogenous inhibitors, namely IL-1 receptor 2 (IL-1R2), which is related to the IL-1R1 and lacks a cytoplasmic domain, and IL-1 receptor antagonist IL-1Ra, which mimics the binding of IL-1β to IL-1R1 but fails to recruit the IL-1RAcP, preventing downstream signaling. xref "
sparser
"One study reported direct binding of IL-1β to integrin α5β1 xref , however our data suggest activation of α5β1 is likely to occur downstream of IL-1β binding to IL-1R. Prior blocking of IL-1R prevented an increase in vinculin adhesion contacts and prevented the increase in α5β1 localizations and clustering at the membrane."
sparser
"For example, in neurons, binding of IL-1β with IL-1R causes the recruitment of the neuron specific adaptor protein AcPb ( xref ) which mediates NDMR 2b phosphorylation, calcium influx, and excitotoxicity ( xref ); a potential mechanism linking IL-1β overproduction with exacerbated seizures ( xref )."
sparser
"Meanwhile, binding of IL-1β with IL-1R on glia lineage cells recruits the AcP adaptor protein, which is predominantly expressed on astrocytes and microglia, and promotes NF-κB mediated transcription of other inflammatory cytokines such TNF-α ( xref ) and IL-6 ( xref ; xref ; xref ) suggesting that IL-1β plays an executive role in formation of neuroinflammatory responses."
reach
"Collectively, these data show that a factor or factors released into the media of human placental explants prime monocytes for inflammasome induction.To determine whether IL-1β constitutively secreted by placental trophoblasts is responsible for the CM-mediated inflammasome priming in monocytes, we used an antibody that blocks binding of IL-1β to IL-1R and also generated THP-1 cells lacking expression of IL-1R through CRISPR-mediated gene editing (Fig. S3 G)."
reach
"IL-1β can enter the hematopoietic microenvironment of BM with blood circulation, bind to IL-1R on hematopoietic stem cells and hematopoietic progenitor cells in BM and stimulate hematopoietic stem cells and hematopoietic progenitor cells to differentiate into neutrophils and macrophages, which are continuously delivered to the damaged area of the myocardium [19]."
reach
"Mechanistically, upon binding of IL-1α or IL-1β to IL-1R, the signaling adaptor protein myeloid differentiation factor 88 (MyD88) is recruited, initiating sustained activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) via the MyD88-IRAK signaling cascade."