Schuler Marc K, Aicher Wilhelm K
Center for Orthopedic Surgery, UKT University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Rheumatol Int. 2004 Jan;24(1):1-8. doi: 10.1007/s00296-003-0321-4. Epub 2003 Jul 15.
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.
白细胞介素-18（IL-18）是IL-1细胞因子家族的成员，具有促炎活性。在骨关节炎（OA）组织中已检测到IL-18，而在类风湿性关节炎（RA）滑膜组织中的水平更高。因此，我们研究了主要信号转导通路对IL-18表达的作用。在此我们报告，环磷酸腺苷降低，而离子霉素增加RA滑膜成纤维细胞（SF）中IL-18 mRNA的表达，但在OA SF中无此现象。此外，Mas-7激活G蛋白增强了OA SF中IL-18逆转录聚合酶链反应信号，但在RA SF中无此作用。特异性蛋白激酶C激活剂佛波酯肉豆蔻酸酯降低RA SF和OA SF中IL-18的转录和分泌。星形孢菌素改变了IL-18 mRNA的自发水平并增加了IL-18蛋白的分泌。我们得出结论，G蛋白激活和蛋白激酶C激活可能部分导致RA期间IL-18水平升高。
