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KMID : 0388220100170030238
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Journal of the Korean Rheumatism Association
2010 Volume.17 No. 3 p.238 ~ p.245
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IL-15 Induced an Increased SDF-1 Expression in the Synovial Fibroblasts of Patients with Rheumatoid Arthritis
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Park Young-Eun
Kim Sung-Il
Park Seong-Hu
Back Seung-Hoon
Oh Hye-Jwa
Hur Yang-Mi
Cho Mi-La
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Abstract
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Objective: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS).
Methods: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-?B (parthenolide) and activator protein 1 (AP-1, curcumin).
Results: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-?B and AP-1.
Conclusion: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-?B, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.
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KEYWORD
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IL-15, Stromal cell-derived factor-1, IL-17, Fibroblast-like synoviocytes, Rheumatoid arthritis
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