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