Adrenomedullin inhibits IL-1β-induced rheumatoid synovial fibroblast proliferation and MMPs, COX-2 and PGE2 production.
To determine the effects of adrenomedullin (AM) on interleukin (IL)-1β-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-1β 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-1β-induced RASFs proliferation and inhibited MMP-1, 3, COX-2 and PGE2 production. AM (1-52) also inhibited IL-1β-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.
Lee
Eun-Gyeong
EG
Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, Jeonbuk, 561-712, South Korea.
Lee
Sang-Il
SI
Chae
Han-Jung
HJ
Park
Seoung Ju
SJ
Lee
Yong Chul
YC
Yoo
Wan-Hee
WH
D053607:Adrenomedullin / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
C507862:ADM protein, human; D053583:Interleukin-1beta; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053607:Adrenomedullin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020782:Matrix Metalloproteinases; D015232:Dinoprostone