Skip to main content

Laminin, but not lipopolysaccharide, IL-1 or tumor necrosis factor alpha, induces IL-16 gene activity in synovial fibroblasts

In rheumatoid arthritis (RA), synovial fibroblast-like cells (SF) contribute significantly to articular inflammation. They express elevated levels of cytokines and chemoattractant factors, including IL-16. We analyzed the induction pathways for IL-16 mRNA expression in synovial fibroblasts from eight RA patients in comparison with SF from six osteoarthritis (OA) patients and dermal fibroblasts (DF) (n = 6) by real-time quantitative RT-PCR. Stimulation of cAMP-dependent signal transduction by forskolin induced a twofold and 2.5-fold enhancement of IL-16 RT-PCR signals in DF and OA-SF, respectively, whereas the kinase inhibitor staurosporine induced IL-16 transcripts to a lesser extent in DF and OA-SF. In contrast, in RA-SF, staurosporine significantly augmented IL-16 RT-PCR signals (2.7-fold, P < 0.022), but forskolin failed to do so (1.3-fold, P < 0.15). Phorbol ester induced IL-16 mRNA only in RA-SF (1.5-fold) but not in OA-SF, and reduced IL-16 signals in DF (0.6-fold). Most interestingly, growth of cells on laminin significantly induced the expression of IL-16 mRNA (1.88-fold, P < 0.001). Collagen and other matrix proteins had no such effects. Induction of IL-16 mRNA by laminin was more pronounced in RA-SF than in OA-SF. Addition of lipopolysaccharide (LPS) to SF induced different cytokines including IL-1a, IL-1b, IL-6 and IL-8, but not IL-16, indicating that induction of IL-16 mRNA by laminin was not a LPS artifact. Addition of IL-1b or tumor necrosis factor alpha did not upregulate IL-16 mRNA, indicating that the NF-κB and p38 pathways are not the main activators of the IL-16 gene. We conclude that OA-SF and RA-SF differ in their IL-16 mRNA responses, in that OA-SF respond primarily to adenylate cyclase-dependent pathways while RA-SF respond prominently to protein kinase pathways. Laminin activates the IL-16 gene in synovial fibroblasts but this activation is not dependent on NF-κB or p38 signal transduction.

Acknowledgement

The project was supported by DFG grant Ai 16/14-1

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Aicher, W., Alexander, D., Pap, T. et al. Laminin, but not lipopolysaccharide, IL-1 or tumor necrosis factor alpha, induces IL-16 gene activity in synovial fibroblasts. Arthritis Res Ther 5, 145 (2003). https://doi.org/10.1186/ar946

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/ar946

Keywords

  • Laminin
  • Forskolin
  • Dermal Fibroblast
  • Staurosporine
  • Synovial Fibroblast