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AB0100 IL-22-Mediated BCL-2 Expression in Rheumatoid Arthritis Fibroblast-like Synoviocytes through STAT3 Activation
  1. M. Liu,
  2. Y. Pan,
  3. Y. Liu,
  4. Y. Wu,
  5. M. Yang,
  6. B. Mo
  1. Rheumatology, The Third Affiliated Hospital to Sun-Yet San University, Guangzhou, GuangDong Province, China

Abstract

Background Interleukin-22 (IL-22) is a novel cytokine that is mostly produced by T cells and innate lymphoid cells but selectively stimulates non- immune cells, which immediately caught the attention of many fields such as tumor, chronic inflammatory disease and infectious disease. Considering the persistent biological abnormalities in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and transient effects of current best treatment such as anti-TNF biologics, other cytokines might be involved and we focus here on the role of IL-22.

Objectives To test the effect of IL-22 on the survival of RA-FLSs and to investigate whether signal transducer and activator of transcription 3 (STAT3) is implicated in this process.

Methods Bcl-2 mRNA and Bcl-xL mRNA expression in the RA-FLSs, osteoarthritis-FLSs and trauma-FLSs were determined using the Real-time quantitative polymerase chain reaction (RT-qPCR), Bcl-2 protein expression in FLSs were detected by the Western Blotting analysis. The effects of recombinant human interleukin-22 (rhIL-22) at concentrations of 0, 1, 10, 100 ng/mL and STA-21 (a STAT3 inhibitor at concentrations of 0, 25μM, 50μM) on the protein levels of Bcl-2 and p-STAT3 in the RA-FLSs were determined by Western blotting analysis. RA-FLSs were co-cultured with rhIL-22 in the presence or absence of STA21 for 24 h, and the protein levels of Bcl-2 and p-STST3 were evaluated by Western blotting analysis.

Results The anti-apoptotic Bcl-2 (P<0.05) and Bcl-xL (P<0.01) are increased in RA-FLSs compared with osteoarthritis-FLSs and trauma-FLSs, and so is Bcl-2 protein (P<0.01). IL-22 increased, and STA-21 decreased the protein levels of Bcl-2 and p-STAT3 (IL-22: FBcl-2=48.63, PBcl-2<0.01; FP-STAT3=25.7, PP-STAT3<0.01 STA-21: FBcl-2=49.74, PBcl-2<0.01l; FP-STAT3=109.97, PP-STAT3<0.01) in the RA-FLSs obviously. Additionally, treatment with STAT3 inhibitor STA-21 reversed the effect of IL-22-induced Bcl-2 upregulation in the RA-FLSs (FBcl-2=84.67, PBcl-2<0.01; FP-STAT3=82.46, PP-STAT3<0.01).

Conclusions STAT3 is critical in the process which IL-22-induced Bcl-2 upregulation in the RA-FLSs. The effects of IL-22/STAT3 confer on them the potential to be used for therapeutic applications in RA.

Disclosure of Interest None declared

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