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AB0040 Il-29 induces production of il-6 and il-8 in rheumatoid arthritis synovial fibroblasts via jak/stat3 and mapk/nf-kb signaling pathways
  1. F. Wang1,
  2. L. Xu2,
  3. X. Feng2,
  4. W. Tan2,
  5. M. Zhang2
  1. 1Cardiology
  2. 2Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Abstract

Background IL-29 (Interferon Lambda 1)is a newly described member of the interferon family, which binds to its receptor to activate JAK-STAT, MAPK or Akt signaling pathways to induce antiviral, antiproliferative, antitumor and immune responses. The immunoregulatory role of IL-29 in immune cells is still poorly understood. We previously reported that IL-29 levels were abnormally elevated in patients with rheumatoid arthritis (RA); however, the role of IL-29 in RA inflammation remains unknown.

Objectives To investigate the effect and pathway of IL-29 on the production of proinflammatory cytokines IL-6 and IL-8 in RA synovial fibroblasts (RA-FLS).

Methods Human RA synovial fibroblast cell line, MH7A cells, were stimulated with IL-29 with or without inhibitors of MAPK/NF-κB and JAK/STAT3, the production of IL-6 and IL-8 was examined by real time PCR and enzyme-linked immunosorbent assay (ELISA). The phosphorylation of JNK, P38, ERK, IκB, NF-κB and STAT 3 was detected by western blot.

Results IL-29 enhanced the production of IL-6 and IL-8 in MH7A cells in a dose-dependent manner. IL-29-mediated induction of IL-6 and IL-8 was transduced via activation of phosphorylation of JNK, P38, ERK, IκB, NF-κB and STAT3.

Conclusions RA inflammation can be amplified by enhanced IL-29-mediated proinflammatory cytokine production on synovial fibroblasts. Our results provide the initial evidence that IL-29 may be a new target in the prevention of inflammation and joint destruction in RA.

References Wang F, Xu L, Feng X, Guo D, Tan W, Zhang M. Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis. Arthritis Res Ther, 2012. 14(5): R228.

Acknowledgements This project was sponsored by the grants from the National Natural Science Foundation of China (No. 30901332, 81172845, 81273294); the Key Project of the Natural Science Foundation of Jiangsu Province, China (No. BK2011851, BK2012875); the Graduate Innovation Project of Jiangsu Province, China (No. CXZZ11-0701) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Disclosure of Interest None Declared

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