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Interleukin-18 is regulated by G protein pathways and protein kinase signals in human fibroblasts

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Abstract

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.

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Acknowledgements

We thank Drs. S. Sell and F. Martini for tissue samples, as well as T. Müller and A. Hack for their excellent technical service. This project was supported in part by a Fortüne grant (F 411).

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Authors and Affiliations

  1. Center for Orthopedic Surgery, UKT University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany

    Marc K. Schuler & Wilhelm K. Aicher

  2. Research Laboratory, Center for Orthopedic Surgery, Pulvermühlstrasse 5, 72070, Tübingen, Germany

    Wilhelm K. Aicher

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  1. Marc K. Schuler
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  2. Wilhelm K. Aicher
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Correspondence to Wilhelm K. Aicher.

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Schuler, M.K., Aicher, W.K. Interleukin-18 is regulated by G protein pathways and protein kinase signals in human fibroblasts. Rheumatol Int 24, 1–8 (2004). https://doi.org/10.1007/s00296-003-0321-4

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  • DOI: https://doi.org/10.1007/s00296-003-0321-4

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