IndraLab

Statements


1 2 2 | 13 121

sparser
"IL-1Ra binds to IL-1R1 and competitively blocks IL-α and IL-1β [ xref ]."

sparser
"The stable complex of IL-1Ra-ABD with IL-1R established the absence of steric hindrance due to the addition of ABD to IL-1Ra."

sparser
"Thus, in our study the binding of IL-1ra by sIL-1RI may be allowing the IL-1β-mediated effects."

sparser
"In contrast, most of the interactions of antagonist IL-1Ra with IL-1R1 (PDB entry 1IRA) are established with domains D1 and D2, exhibiting only a few contacts with D3 [ xref ]."

sparser
"IL-1ra binds to IL-1R as a competitive inhibitor of IL-1 binding, without inducing cellular responses after ligation."

sparser
"This way, antagonist IL-1Ra binds to IL-1R, inhibiting cytokines IL-1α and IL-1β."

sparser
"The IL-1Ra binds to IL-1R, blocking its interaction with IL-1 and inhibiting IL-1-mediated signal transduction."

sparser
"The IL-1 signaling pathway is tightly regulated at multiple levels, including extracellularly by the decoy receptor IL-1R2, which lacks a cytoplasmic domain and therefore binds IL-1 (with a greater affinity for IL-1β than IL-1α) without activating a cellular response [ xref , xref , xref ], and the competitive antagonist IL-1Ra, which binds IL-1R1 with high affinity, blocking the binding of IL-1 [ xref ]."

sparser
"The rationale for testing the ability of the IL-1Ra to block the responses provides indirect evidence that precursor IL-1α, mature IL-1α, and mature IL-1β share the same receptor since IL-1Ra binds solely to IL-1R1."

sparser
"IL-1Ra binds with a high affinity to IL-1R1 [12] , but, despite similar binding affinity, the two IL-1 agonists and IL-1Ra interact differently with IL-1R1."

sparser
"IL-1R1 can also bind to IL-1Ra, which does not produce a signal due to its lack of an IL-1 receptor accessory protein interaction domain, thereby acting as a competitive binding factor to inhibit proinflammatory signaling [ xref ]."

sparser
"IL-1Ra binds the receptor IL-1R1 with affinity higher than that of IL-1α or IL-1β, but it does not trigger the association of IL-1 receptor accessory protein, thus there is no activation of the IL-1 signaling [ xref ]."

sparser
"When IL-1Ra binds to the corresponding IL-1R, the interaction of IL-1 and IL-1R is blocked."

sparser
"IL-1ra binds to IL-1R1 with an affinity that is 100–500 times higher than for IL-1R2 and competitively inhibits IL-1α/β binding to the receptor."

sparser
"Moreover, the soluble form of IL-1R1 and IL-1RA have the highest capacity to prevent IL-1α while IL-1R2 and IL-1R1 and IL-1RA have a similar capacity to prevent IL-1β signaling."

sparser
"In contrast to IL-1β, IL-1RA binds to IL-1R1 to inhibit IL-1 signaling xref , xref ."

sparser
"IL-1 signaling can be blocked by IL-1ra which binds to the IL-1R and blocks signal transduction [ xref ]."

sparser
"IL-1RA binds to IL-1R1 with equal or greater affinity than IL-1α and IL-1β but does not activate downstream signaling ( xref , xref , xref )."

sparser
"IL-1Ra can competitively bind with IL-1R1 against IL-1β or IL-1α."

sparser
"For example, in two separate datasets pertaining to breast cancer, IL1RNIL1R1 was responsible for 3,779 and 1,445 new cases, respectively."

sparser
"Binding of IL-1RA to IL-1R1 leaves IL-1R1 unable to recruit IL-1R accessory protein for the transduction of IL-1-mediated actions [ xref ]."

sparser
"When IL-1Ra binds to IL-1R1 ( xref ), the conformational change (shown in xref ) does not result IL-1R3 binding."

sparser
"IL-1RA can also bind IL-1R1 and prevent the recruitment of the co-receptor, acting as an antagonist."

sparser
"IL-1Ra binds non-productively IL-1R preventing cell signaling effects of IL‐1α and IL-1β and antagonizes the pro-inflammatory response [52] ."

sparser
"Conversely, in the interaction model of IL-1R3 with the IL-1RaIL-1R1 complex, only domain 2 of IL-1R3 establishes contact, resulting in an unstable interaction ( xref )."

sparser
"Furthermore, the formation of the IL-1Ra-IL-1R1 complex induces a distinct conformational change compared to that which occurs upon IL-1α/β binding."

sparser
"We further characterized the sizes and binding of IL-1raBF and sIL-1RI to IL-1ra by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate, ligand binding interference analyses, N-glycosidase treatment, concanavalin A affinity chromatography, and with the use of monoclonal antibodies (mAb) to human recombinant IL-1ra."

sparser
"The antagonist IL-1Ra also binds IL-1R1, competing with agonist IL-1 ligands and preventing the formation of the signalling complex ( xref )."

sparser
"The low affinity for IL-1ra is consistent with the idea that both of these molecules serve to regulate the activity of IL-1?; if IL-1ra bound well to the type II IL-1R, they would negate each other's [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Both cytokines signal through IL-1R1 and its accessory protein IL-1R3, which can be efficiently inhibited by IL-1Ra that competitively binds IL-1R1 but does not recruit the accessory protein [ xref ]."

sparser
"39 Mutating the Lys131 to glutamine destabilized the interaction of IL-1R1 and IL-1Ra with a ΔΔG of 0.6308 kcal/mol, as predicted by Fold-X ( Figure S3 B)."

sparser
"Both co-immunoprecipitation ( Figure 3 A) and pull-down assay ( Figure S3 C) demonstrated that the K131E substitution impaired the interaction between IL-1R1 and IL-1Ra, but not between IL-1R1 and IL-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The KD values of wild-type (WT) and K131E mutant IL-1R1 binding to IL-1Ra were 3.690 × 10 −11 and 1.415 × 10 −9 M, respectively, confirming the reduced binding affinity of the mutant IL-1R1 to its ant[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Anakinra as IL-1RA binds to the IL-1R and consequently prevents the binding of IL-1α as well as IL-1β to IL-1R1 and blocks their activity [110,111]."

sparser
"These biologic agents target the blockade of pro-inflammatory cytokines such as IL-1 (anakinra-IL-1R antagonist), (canakinumab, rilonacept- anti-IL-1β monoclonal antibody), IL-6 (tocilizumab) and TNF (etanercept, infliximab)."

sparser
"According to the Fold-X prediction, Lys131 substitutions to negatively charged amino acids Glu (E) or Asp (D) requires excessive energy compared with positively charged amino acids His (H) or Arg (R),[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In summary, IL-1 molecules (IL-1α and IL-1β) are prototypic proinflammatory cytokines that play a role in inflammatory processes by combining to the IL-1 receptor (IL-1R), whereas their antagonist, IL-1Ra, binds to IL-1R1, inhibiting the integration of IL-1R1 with IL-1α and IL-1β ( xref )."

sparser
"The disrupted interaction between IL-1R1 K131E or K131D and IL-1Ra was demonstrated by co-immunoprecipitation ( Figure 4 C)."

reach
"Anakinra, a recombinant form of IL-1Ra, directly binds to and blocks IL1R1."

sparser
"The patient is able to rope skipping after treatment with canakinumab for 3 months, related to Figure 6 The effect of this IL-1R1 mutation demonstrates the importance of the interaction between IL-1R[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The substitution of a basic, polar amino acid at residue 131 with an acidic amino acid disrupted the interaction of IL-1R1 with IL-1Ra."

sparser
"Our results demonstrated that K131E substitution on IL-1R1 leads to the constitutive inflammation by impairing the interaction between IL-1R1 and IL-1Ra."

sparser
"IL-1Ra binds to IL-1R1 with comparable affinity to IL-1α and IL-1β but fails to induce the conformational change in the receptor that is required for the recruitment of the IL-1RAcP co-receptor and signal transduction [ xref , xref ]."

sparser
"51 Our data suggested that the charge stability of lysine 131 in IL-1R1 is critical for the interaction of IL-1R1 with IL-1Ra."

sparser
"52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 However, all the associated SNPs are either located in the noncoding region (intergenic/intronic/UTR) of IL1RN gene or are synonymous variants, which do not affec[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"IL-1Ra (MW ~ 17.6 kDa), a receptor antagonist of IL-1, can competitively bind with IL-1R1 thereby blocking cell activation by the cytokine [ xref ]."

sparser
"IL-1R1 is the signalling receptor, which binds IL-1 and recruits the accessory chain IL-1R3 for initiating signalling, while the IL-1-like soluble antagonist IL-1Ra binds to IL-1R1, thereby preventing binding of agonist IL-1 molecules, and does not allow association of IL-1R3, thus inhibiting signal transduction."

sparser
"IL-1Ra binds IL-1R1, competitively inhibiting the binding and activities of IL-1β and IL-1α."

sparser
"IL-1Ra binds IL-1R1 with an affinity higher than that of IL-1 but fails to recruit the IL-1RAcP."

reach
"The receptor IL1R1 binds IL-1α, IL-1β, and IL1RN."

sparser
"IL-1Ra binds to IL-1R1 but does not recruit the accessory chain IL-1R3 and does not initiate signal transduction [28] ."

sparser
"The crystal structure of the IL-1R1IL-1Ra complex showed that IL-1Ra binds at the large groove area between D1 and D2, but it fails to interact with the small area on D3 [31] ."

reach
"Notably, the opposite (protective) allele IL1RN * 2 has been previously associated with higher IL-1Ra and lower IL-1beta release XREF_BIBR."

sparser
"In the case of the IL-1RaIL-1R1 complex, the accessory chain IL-1R3 fails to be recruited, and therefore signalling does not occur [28] ."

sparser
"As a control, the same attempt was made on the crystal structure of IL-1R bound to IL-1ra and, as expected, no interaction could be calculated (data not shown)."

sparser
"The same studies shows that in the model of IL-1R3 interacting with the IL-1RaIL-1R1 complex, only domain 2 of IL-1R3 can take contact, resulting in unstable interaction."

sparser
"In vivo, IL-1ra binds to IL-1R1 without protein dimerization, thus inhibiting downstream activities [ xref ]."

reach
"For instance, anakinra binds to IL-1R1 and inhibits its interaction with IL-1β."

sparser
"IL-1R1 can also bind the antagonist IL-1Ra, which blocks the formation of the signalling complex thereby inhibiting IL-1-induced receptor-mediated inflammatory activation."

sparser
"For example, ANXA1-FPR1 system is potent effective mediators in anti-inflammatory processes xref , and their interaction was lost between CECs and ImCs in KC samples; IL1RN-IL1R1 are natural anti-inflammatory cytokines xref , and their interaction were eliminated between CECs and CSCs in KC samples."

sparser
"IL-1RA binds to IL-1R1 with similar affinity to its biologically active counterparts, though binding fails to initiate downstream, intracellular signaling [ xref ]."

sparser
"IL-1Ra binds the receptor IL-1R1 with a higher affinity than IL-1α or IL-1β, although without activation of the IL-1 signaling [ xref ]."

sparser
"We spotted that ANXA1-FPR1, and IL1RN-IL1R1, whose anti-inflammatory roles have been reported, were erased in KC samples, implying their impact on the increased inflammation in keratoconus."

sparser
"In this disease, the mutation characteristically disrupts the interaction of IL-1R1 with IL-1Ra."

sparser
"While IL-1R1 binds with IL-1Ra involving small conformational changes of the D3 domain [ xref ], significant changes were found when IL-1R1 binds with a peptide antagonist (AF10847)[ xref ]."

sparser
"IL-1Ra binds to the IL-1R1 but fails to induce recruitment of the co-receptor IL-1R3 (aka IL-1RAcP), thus preventing signal transduction via the IL-1R. This is how it works as a competitive antagonist for both IL-1α and IL-1β."

reach
"Anakinra exerts its anti-inflammatory effects by binding to the IL-1R, which inhibits the interaction of both IL-1α and IL-1β with the receptor."

sparser
"IL-1Ra binds to IL-1R1 with a high affinity and inhibits IL-1α or IL-1β function ( xref )."

sparser
"Since IL-1Ra binds to IL-1R1 (common receptor for both IL-1β and IL-1α) ( xref ), it may inhibit the function of IL-1β and IL-1α cytokines."

sparser
"IL-1RA mainly binds IL-1R1, having little effect on IL-1R2, which is in agreement with their action as IL-1 inhibitor molecules [ xref ]."

reach
"Patients suffering from AID caused by increased IL-1β signaling showed good response with anakinra, rilonacept (recombinant IL-1 receptor IL-1R that binds to IL-1α, IL-1β, and IL-1RA), and canakinumab (human monoclonal antibody that binds to IL-1β) (Georgin-Lavialle et al., 2019; Blackstone et al., 2023)."

sparser
"IL-1Ra competitively binds to IL-1R1, thereby blocking binding of IL1α and IL1β [ 82 ]."

sparser
"IL-1Ra binds to IL-1R1 without signaling and blocks binding of IL-1α/β xref ( xref )."

sparser
"Anakinra as IL-1RA binds to the IL-1R and consequently prevents the binding of IL-1α as well as IL-1β to IL-1R1 and blocks their activity [ xref , xref ]."

sparser
"Since IL-1RA interacts with IL-1R1, IL-1RAP, and the IL- 1R1+IL-1RAP complex (Fig. 1), three-dimensional structures of the corresponding proteins were required for modeling and analysis."

sparser
"Modeling IL-1RA interactions with IL-1R1"

sparser
"IL-1Ra binds to the same IL-1R1 as IL-1α and IL-1β, thus limiting the pro-inflammatory signaling that these cytokines induce ( xref ; xref )."

reach
"IL-1RN inhibits the activities of IL-1alpha and IL-1beta by binding to receptor IL1R1."

sparser
"The availability of anakinra, a nonglycosylated recombinant human IL-1Ra that binds to IL-1R1 competitively inhibiting IL-1 signaling, provides an interesting and safe tool for therapeutic intervention."

sparser
"IL-1Ra bound IL-1R1 cannot productively signal through IL-1R3."

sparser
"Modeling interaction of standard IL-1RA with IL-1R1."

sparser
"According to the contact list of template residues, serine at position 130 of the IL-1RA molecule binds to leucine at position 237 of IL-1R1 (see Table 4)."

sparser
"Modeling interaction of IL-1RA with the rs315952 polymorphism with IL-1R1."

sparser
"Thus, based on the interactions of IL-1RA with the rs315952 polymorphism with IL-1R1, we cannot draw a definitive conclusion regarding the polymorphism’s impact on its involvement in initiating the IL-1 signaling pathway."

sparser
"In addition, five amino acids are crucial for the interaction of IL-1RA with IL-1R [ xref ]."

sparser
"IL-1Ra is able to bind to the IL-1R with similar affinity as IL-1α and IL-1β and inhibit IL-1 activity."

sparser
"IL-1Ra binds IL-1R, making the receptor unavailable for binding IL-1α, without activating the IL-1α pathway, whereas the anti-IL-1α antibody sequesters unbound IL-1α and prevents it from binding to the receptor."

sparser
"Meanwhile, IL-1Ra competitively binds to IL-1R1, effectively blocking the interaction and subsequent signaling of IL-1α and IL-1β [ xref , xref ]."

sparser
"However, it was postulated that TLR4 activation in M1-like macrophages could suppress the production of an endogenous inhibitor of IL-1β, IL1Ra, which competitively binds to IL1R against IL-1β ( xref ), while in our study, we observed that SBP2 had the minimal effect of IL1Ra production in MMe."

sparser
"The results showed that the competitive binding of IL-1Ra to the IL-1R reduced the recruitment of macrophages and the phagocytosis of copper ions triggers intracellular ROS production, leading to macr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"However, against this hypothesis is our observation that IL-1Ra was able to antagonize LPS-driven inflammation, which itself requires the binding of IL-1Ra to type I IL-1R."

sparser
"This is exemplified for IL-1RA [ 33 , 34 ], which binds to IL-1R1 with the same affinity than IL-1 [ 35 ]."

sparser
"IL-1Ra binds to IL-1R1, and this cytokine work as the inhibitor of IL-1α and IL-1β ( xref , xref ) ( xref )."

sparser
"IL1RA binds to the interleukin 1 receptor type 1 (IL1R1) and blocks its activation."

sparser
"IL-1Ra binds IL-1R1 without recruitment of IL-1RAcP, resulting in the inhibition of IL-1α and IL-1β binding in a competitive manner."

sparser
"A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1."

reach
"On the mRNA level of MSC, we found IL1RN, which binds to IL1R on the cell surface with subsequent inhibition of the IL1beta signaling pathway, to be upregulated from a low basal level of expression upon stimulation with the PTC (318-fold) or IL1beta (107-fold) and to remain unchanged after stimulation with IL6, IL8, C3a and C5a in concentrations used in the " cocktail " (XREF_FIG)."

sparser
"IL-1Ra binds with IL-1R [ xref , xref ], and IL-1R signaling is critical for neutrophil function [ xref , xref , xref ]."

sparser
"Moreover, IL-1RA can also bind IL-1R1 without inducing an activator signal, taking the place of IL-1β [ xref , xref ]."

sparser
"As an antagonist, binding of IL-1Ra to IL-1R1 prevents its coupling with IL-1RAcP and further signaling."

sparser
"This may be because IL-1RA directly binds IL-1R, but not IL-1β, to block the biological effects of IL-1β."

sparser
"IL-1Ra competitively binds to IL-1R1 but does not have the capacity to activate IL-1 signaling."

sparser
"IL-1Ra binds to IL-1R on ECs and prevents proinflammatory events initiated by an IL-1 β  : IL-1R interaction, including enhanced influx of neutrophils, macrophages, and lymphocytes in inflamed lungs [ xref ]."

sparser
"In addition, the receptor antagonist IL-1Ra can bind to IL-1R1, and thereby prevents the formation of the IL-1R complex [ xref ]."

sparser
"IL-1RA binds to IL-1R with a high affinity and competitively interferes with the binding of IL-1 to IL-1R as an inhibitory protein for IL-1 activity."

reach
"Anakinra binds IL-1R1 blocking both IL-1α and IL-1β actions."

sparser
"Currently, several commercially available drugs target the IL-1 pathway, such as anakinra (IL-1RA that binds to IL-1R1), canakinumab (a human monoclonal IgG1 antibody for blocking IL-1β), rilonacept (a soluble decoy fusion protein that competitively binds to IL-1R) and gevokizumab (a humanized monoclonal anti-IL-1β) ( xref )."

sparser
"IL-1Ra binds to IL-1R1, but is unable to activate the IL-1 intracellular signaling pathways [ xref ]."

sparser
"While IL-1 binding induces receptor signaling through additional binding to the IL-1 receptor accessory protein, IL-1Ra solely binds the IL-1R1 and, thus, acts as a competitive inhibitor."

reach
"Both IL-1RA and anakinra bind to the IL-1R in the same manner and interfere with the binding of IL-1α and IL-1β, thereby blocking their activity.Anakinra is administered subcutaneously (SC) in a daily injection containing 100 mg/0.67 mL solution."

reach
"Thus, the availability of IL1R2 transcripts for analyses in this study may have been diluted by mRNA transcripts produced by the other cell types.Functional IL-1RN binds to IL-1R and inhibits interact[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"IL-1Ra binds to IL-1R1 but unlike IL-1α or IL-1β, the binding of IL-1Ra to IL-1R1 does not result in signaling."

sparser
"Functional IL-1RN binds to IL-1R and inhibits interaction of IL-1 α and IL-1 β signaling ligands with the receptor ( Seckinger et al., 1987 )."

sparser
"Firstly, we examined the expression levels of IL1A, its receptor IL1R1, and the antagonist IL1R1-IL1RN in four cell types ( xref a)."

sparser
"Recombinant human IL-1Ra (rhIL-1Ra) as a genetically engineered drug has been found to have the same biological function as natural IL-1Ra both of which can bind specifically to IL-1R to inhibit various inflammatory diseases, like encephalomyelitis [ xref ], intestinal mucositis [ xref ], arthritis [ xref ], and even cancer [ xref , xref ]."

reach
"However, anakinra can inhibit the activity of IL-1α and IL-1β by binding to IL-1R [41], thereby reducing the inflammatory response and tissue damage caused by IL-1 (Fig. 1, created with biorender.com)."

sparser
"With high affinity, IL-1Ra binds to IL-1R1 and, thus, inhibits IL-1α or IL-1β activity [ xref ]."

sparser
"IL-1ra binds to the IL-1R but exerts no biological activity and therefore functions as a competitive inhibitor of IL-1 signaling."

sparser
"IL-1 signaling can be inhibited by the endogenous ligand IL-1Ra, which can bind to IL-1R1 without inducing the dimerization with IL-1RAcP resulting in prevention of IL-1 signaling [60] ."

sparser
"It has been established that IL-1Ra binds to IL-1R1 and thus antagonizes biological effects of IL-1 [ xref ]."

sparser
"IL-1Ra binds IL-1R, blocks IL-1R association with the accessory protein IL-1RAcP, and thereby interferes with IL-1 binding to the receptor."

sparser
"IL-1Ra competitively binds to IL-1R1, thereby impeding the ability of IL-1β and IL-1α to bind to and signal through the receptor."

sparser
"PE increases the expression of IL-1Ra in the CNS, which leads to the binding of IL-1Ra to IL-1R expressed on microglia, which inhibits the activity of IL-1α or IL-1β and thereby reduces microglial activation ( xref )."

sparser
"IL-1Ra binds with IL-1R [ xref , xref ], and IL-1R signaling is critical for neutrophil function [ xref , xref , xref ]."

sparser
"IL-1Ra, which binds to IL-1Rs without transmitting an activation signal, represents a physiological inhibitor of pre-formed IL-1."

sparser
"It is possible that IL-1RA may bind to IL-1R, modulating NFκB pathway members xref , altering the phosphorylation status of AR, and ultimately leading to AR stabilization."

sparser
"Firstly, IL-1RA competitively binds to the IL-1R1 with a high affinity to prevent its binding with agonistic ligands."

sparser
"In contrast, anti-inflammatory IL-1RA binds to the IL-1R1 and blocks signaling events due to its lack of an essential IL-1R accessory protein (Tack et al., xref )."

sparser
"IL-1Ra binds to IL-1R with an avidity equal to that of IL-1 but fails to stimulate the cells, thus functioning as an inhibitor of IL-1 binding."

sparser
"There are a limited number of anti-inflammatory therapies that target IL-1 signaling; this includes anakinra (commercially known as Kineret), a recombinant form of IL-1Ra that binds competitively to IL-1R and non-selectively blocks downstream signaling [ xref ]."

sparser
"IL-1RA is structurally related to IL-1α and IL-1β (described above) and binds the shared IL-1R1 with similar high affinity as IL-1β."

sparser
"However, subtle structural differences between IL-1β and IL-1RA result in the inability of the co-receptor IL-1RacP to be recruited to the complex following binding of IL-1RA to IL-1R1 [ xref ]."

sparser
"Polymorphisms in the IL-1β, IL-1RA, or IL-1R genes (as well as IL-6) have been reported in children with FS xref and could result in the following pro-convulsant circumstances: excessive 1L-1β release with saturation of IL-1Rs, defective IL-1RA production, inadequate IL-1RA release, defective IL-1RA binding to IL-1R. These genetic variations could provide yet another explanation for some of the extreme variability in the absolute cytokine levels in seen in our subjects."

sparser
"IL-1Ra competitively binds to the IL-1R1, receptor of IL-1beta, and blocks its activation ( Palomo et al., 2015 ) However, elevated levels of IL-1Ra were shown to be associated with increased risk of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"