AB0100 IL-22-Mediated BCL-2 Expression in Rheumatoid Arthritis Fibroblast-like Synoviocytes through STAT3 Activation. (15th July 2016)

• Record Type: Journal Article
• Authors: Liu, M.; Pan, Y.; Liu, Y.; Wu, Y.; Yang, M.; Mo, B.
• Is Part Of: Annals of the rheumatic diseases. Volume 75(2016)Supplement 2
• Page Start: 931
• Page End: 931
• Publication Date: 2016-07-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2016-eular.5164
• Languages: English
• ISSNs: 0003-4967

Abstract

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: F Bcl-2 =48.63, P Bcl-2 <0.01; F P-STAT3 =25.7, P P-STAT3 <0.01 STA-21: F Bcl-2 =49.74, P Bcl-2 <0.01l; F P-STAT3 =109.97, P P-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 ( F Bcl-2 =84.67, P Bcl-2 <0.01; F P-STAT3 =82.46, P P-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