The Journal of the Korean Rheumatism Association 2010; 17(3): 238-245
Published online September 30, 2010
© Korean College of Rheumatology
박영은1ㆍ김성일1ㆍ박성후1ㆍ백승훈1ㆍ오혜좌2ㆍ허양미2ㆍ조미라2
부산대학교 의학전문대학원 내과학교실1, 가톨릭대학교 류마티스연구센터2
Correspondence to : Sung-Il Kim
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-ՊB (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-ՊB 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-ՊB, 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.
Keywords IL-15, Stromal cell-derived factor-1, IL-17, Fibroblast-like synoviocytes, Rheumatoid arthritis
The Journal of the Korean Rheumatism Association 2010; 17(3): 238-245
Published online September 30, 2010
Copyright © Korean College of Rheumatology.
박영은1ㆍ김성일1ㆍ박성후1ㆍ백승훈1ㆍ오혜좌2ㆍ허양미2ㆍ조미라2
부산대학교 의학전문대학원 내과학교실1, 가톨릭대학교 류마티스연구센터2
Young-Eun Park1, Sung-Il Kim1, Seong-Hu Park1, Seung-Hoon Baek1, Hye-Jwa Oh2, Yang-Mi Heo2, Mi-La Cho2
Department of Internal Medicine, School of Medicine, Pusan National University, Busan1, The Rheumatism Resarch Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul2, Korea
Correspondence to:Sung-Il Kim
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-ՊB (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-ՊB 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-ՊB, 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.
Keywords: IL-15, Stromal cell-derived factor-1, IL-17, Fibroblast-like synoviocytes, Rheumatoid arthritis
Ji Hun Kim, Han Na Choi, Si Hye Kim, Hwajeong Lee, Sung-Hoon Park, Seong-Kyu Kim, Jung-Yoon Choe, Hyun-Hee Kwon, Hee-Jin Cheong
J Rheum Dis 2013; 20(2): 87-93Yong-Jin Kwon, Soo-Jin Chung, Tae-Yeon Kim, Min-Chan Park
The Journal of the Korean Rheumatism Association 2010; 17(2): 153-161Yang Mi Her, Sung-Hwan Park, Mi Kyung Park, Hye-Jwa Oh, Kwi Young Kang, Mi-La Cho
The Journal of the Korean Rheumatism Association 2009; 16(2): 123-132