Interleukin-18 is regulated by G protein pathways and protein kinase signals in human fibroblasts.
Interleukin-18 (IL-18) is a member of the IL-1 cytokine family and has proinflammatory activity. It has been detected in osteoarthritic (OA) and at higher levels in rheumatoid arthritic (RA) synovial tissue. Therefore we investigated major signal transduction pathways for their contribution to IL-18 expression. Here we report that cyclic adenosine monophosphate reduced and ionomycin increased IL-18 mRNA in RA synovial fibroblasts (SF) but not in OA SF. Moreover, activation of G-proteins by Mas-7 augmented IL-18 reverse transcriptase polymerase chain reaction signals in OA SF but not in RA SF. Specific protein kinase C activator phorbol myristate acetate reduced transcription and secretion of IL-18 in RA SF and OA SF. Staurosporine changed spontaneous IL-18 mRNA levels and increased the secretion of IL-18 protein. We conclude that G-protein activation and protein kinase C activation might partially be responsible for elevated IL-18 levels during RA.
Schuler
Marc K
MK
Center for Orthopedic Surgery, UKT University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Aicher
Wilhelm K
WK
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C084070:Mas7 protein, synthetic; D010455:Peptides; D012333:RNA, Messenger; D015759:Ionomycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate