Differential effects of anti-IL-1R accessory protein antibodies on IL-1alpha or IL-1beta-induced production of PGE(2) and IL-6 from 3T3-L1 cells.
Soluble or cell-bound IL-1 receptor accessory protein (IL-1RAcP) does not bind IL-1 but rather forms a complex with IL-1 and IL-1 receptor type I (IL-1RI) resulting in signal transduction. Synthetic peptides to various regions in the Ig-like domains of IL-1RAcP were used to produce antibodies and these antibodies were affinity-purified using the respective antigens. An anti-peptide-4 antibody which targets domain III inhibited 70% of IL-1beta-induced productions of IL-6 and PGE(2) from 3T3-L1 cells. Anti-peptide-2 or 3 also inhibited IL-1-induced IL-6 production by 30%. However, anti-peptide-1 which is directed against domain I had no effect. The antibody was more effective against IL-1beta compared to IL-1alpha. IL-1-induced IL-6 production was augmented by coincubation with PGE(2). The COX inhibitor ibuprofen blocked IL-1-induced IL-6 and PGE(2) production. These results confirm that IL-1RAcP is essential for IL-1 signaling and that increased production of IL-6 by IL-1 needs the co-induction of PGE(2). However, the effect of PGE(2) is independent of expressions of IL-1RI and IL-1RAcP. Our data suggest that domain III of IL-1RAcP may be involved in the formation or stabilization of the IL-1RI/IL-1 complex by binding to epitopes on domain III of the IL-1RI created following IL-1 binding to the IL-1RI.
Yoon
Do-Young
DY
Laboratory of Cell and Immunobiochemistry, Department of Bioscience and Biotechnology, Konkuk University, Hwayang Dong 1, Seoul 143-801, Korea.
Dinarello
Charles A
CA
D041721:3T3-L1 Cells; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053582:Interleukin-1alpha / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D010455:Peptides / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D053577:Interleukin-1 Receptor Accessory Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D010455:Peptides; D017472:Receptors, Interleukin-1; D015232:Dinoprostone; D007052:Ibuprofen