Stanniocalcin-1 attenuates collagen-induced arthritis through inhibiting STAT3 phosphorylation and Th17 response

Rheumatoid arthritis (RA) is an autoimmune disease, associated with chronic inflammation and the imbalance of Th17/Treg. Stanniocalcin-1 (STC-1), a glycoprotein, was found to have anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. The present study aimed to investigate the immunomodulatory effect of STC-1 and its potential value in the treatment of RA. Here, a mouse model of collagen-induced arthritis (CIA) was established. Then body weight, joint erythema and swelling were measured in CIA mice with or without STC-1 treatment. Haematoxylin and eosin (H and E) staining was performed to determine histopathological change. Moreover, the percentage of Th17 and Treg cells in the spleen and inguinal lymph nodes (ILNs) and the culture supernatant in polarizing conditions were examined by flow cytometry. Cytokines in serum were detected by ELISA. As a result, the arthritis score, histologic inflammation and cartilage destruction were decreased in CIA mice treated with STC-1. STC-1 increased the level of transforming growth factor-beta and inhibited the expression of interleukin-17. In CIA mice, the percentage of CD4(+)IL-17A(+) cells in the spleen and ILNs were decreased after STC-1 treatment, while the level of CD4(+)Foxp3(+) cells did not change significantly. In vitro, STC-1 inhibited Th17 cell differentiation and STAT3 phosphorylation in CD4(+) T cells under Th17 cell-polarizing conditions. Collectively, the results demonstrated that STC-1 alleviated RA by inhibiting Th17 cell differentiation through regulating STAT3 phosphorylation. STC-1 may be a potential drug for the treatment of RA.

Automated summary

Stanniocalcin-1 (STC-1) has anti-inflammatory, anti-oxidative stress, and anti-apoptosis properties, and it alleviates rheumatoid arthritis (RA) by inhibiting Th17 cell differentiation through regulating STAT3 phosphorylation.