IL-15 Induced an Increased SDF-1 Expression in the Synovial Fibroblasts of Patients with Rheumatoid Arthritis.
10.4078/jkra.2010.17.3.238
- Author:
Young Eun PARK
1
;
Sung Il KIM
;
Seong Hu PARK
;
Seung Hoon BAEK
;
Hye Jwa OH
;
Yang Mi HEO
;
Mi La CHO
Author Information
1. Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea. ksimd@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
IL-15;
Stromal cell-derived factor-1;
IL-17;
Fibroblast-like synoviocytes;
Rheumatoid arthritis
- MeSH:
Arthritis, Rheumatoid;
Enzyme-Linked Immunosorbent Assay;
Fibroblasts;
Humans;
Immunohistochemistry;
Inflammation;
Interleukin-15;
Interleukin-17;
Memory;
NF-kappa B;
Osteoarthritis;
Phosphatidylinositol 3-Kinase;
Phosphatidylinositol 3-Kinases;
Phosphotransferases;
Synovial Membrane;
T-Lymphocytes;
Transcription Factor AP-1
- From:The Journal of the Korean Rheumatism Association
2010;17(3):238-245
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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-kappaB (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-kappaB 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-kappaB, 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.
