Laminin, but not lipopolysaccharide, IL-1 or tumor necrosis factor alpha, induces IL-16 gene activity in synovial fibroblasts
© The Author(s) 2003
Published: 12 September 2003
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.
The project was supported by DFG grant Ai 16/14-1