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KMID : 0380220070400040562
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Journal of Biochemistry and Molecular Biology
2007 Volume.40 No. 4 p.562 ~ p.570
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Differential Effects of Anti-IL-1R Accessory Protein Antibodies on IL-1α or IL-1β-induced Production of PGE2 and IL-6 from 3T3-L1 Cells
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Yoon Do-Young
Dinarello Charles A.
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Abstract
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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 Iglike 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-1β-induced productions of IL-6 and PGE2 from 3T3-L1 cells. Anti-peptide-2 or 3 also inhibited IL-1-induced IL-6 production by 30%. However, antipeptide-1 which is directed against domain I had no effect. The antibody was more effective against IL-1β compared to IL-1α. IL-1-induced IL-6 production was augmented by coincubation with PGE2. The COX inhibitor ibuprofen blocked IL-1-induced IL-6 and PGE2 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 PGE2. However, the effect of PGE2 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.
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KEYWORD
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Cyclooxygenase, Cytokines, IL-1, IL-1RAcP, Iglike domain, Inflammation
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