A novel role of peptidyl-prolyl isomerase-1 as inducer of IL-6 expression in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations affecting different tissues. Pro-inflammatory cytokines, such as interleukin 1β, IL-6 and IFN-g are associated with the SLE progression; however, the precise molecular mechanisms that in occurs improper cytokines production in SLE remain unknown. Autoantibody production and renal disease were evaluated in NZB/W F1 mice treated with a specific Pin1 inhibitor, Juglone. Inhibition of Pin1 activity significantly suppressed the IL-6 expression in NZB/W F1 mice and developed milder renal lesions than the lesions developing in non Juglone-treated mice. We further found that Pin1 inhibitor treatment suppresses B-cell differentiation and T-cell activation in NZB/W F1 lupus mice. Finally, stat3 phosphorylation was decreased in T cells from Pin1inhibitor-treated mice at 40 weeks of age as compared to that from the saline and isotype control mAb treatment groups. This is the first study to demonstrate that Pin1 plays critical roles in SLE development. Pin1 inhibition to the appropriate level might provide a novel therapeutic strategy target for future SLE therapies.