Adrenomedullin Inhibits IL-1 beta-Induced Rheumatoid Synovial Fibroblast Proliferation and MMPs, COX-2 and PGE2 Production

Abstract

To determine the effects of adrenomedullin (AM) on interleukin (IL)-1 beta-induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by RASFs. The RASFs proliferation was evaluated with CCK-8 reagent in the presence of IL-1 beta with/without AM (1-52) and AM inhibitor (AM (22-52)). MMPs, tissue inhibitor of metalloproteinase (TIMP-1), COXs, PGE2 and intracellular mitogen-activated protein kinase (MAPK) signalings, including p-ERK, p-p38, p-JNK were examined by immunoblotting or semiquantitative RT-PCR and ELISA. AM (1-52) inhibited IL-1 beta-induced RASFs proliferation and inhibited MMP-1, 3, COX-2 and PGE2 production. AM (1-52) also inhibited IL-1 beta-induced phosphorylation of ERK-1/2, p38, JNK. AM 22-52 inhibited the effects of AM (1-52) on proliferation of RASFs and production of MMP-1, 3, COX-2 via MAPKs. These results suggest that AM might involved joint destruction in rheumatoid arthritis and indicate that it might be a new therapeutic modality for management of this disease.