 
            IndraLab
Statements
                                      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
                                
                                  
                                
                                
          
          
                                  "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
                                
                                  
                                
                                
          
          
                                  "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
                                
                                  
                                
                                
          
          
                                  "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
                                
                                  
                                
                                
          
          
                                  "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."
          
                              
          
                               
                            
                                      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
                                
                                  
                                
                                
          
          
                                  "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."
          
                              
          
                               
                            
                                      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
                                
                                  
                                
                                
          
          
                                  "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
                                
                                  
                                
                                
          
          
                                  "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 ]."
          
                              
          
                               
                            
                                      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."