Y-27632, a Rho-associated protein kinase inhibitor, inhibits systemic lupus erythematosus

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Yuanyuan Wang, Yang Lu, Jixia Chai, Meiqun Sun, Xiaodong Hu, Wenxin He, Min Ge, Changhao Xie
The purpose of the present study was to evaluate whether Rho-kinase inhibition (Y-27632) modulated the expressions of nuclear factor kappaB (NF-κB) in systemic lupus erythematosus. 20 wild type mice and 20 MRL/lpr mice were applied for the research. The animals were randomly assigned to wild type, wild type+Y-27632 group, MRL/lpr group and MRL/lpr+Y-27632 group. 5mg/kg Y-27632 was intravenously injected to inhibit the ROCK expressions.Y-27632 significantly decreased the serum levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and increased IL-10 level in serum of MRL/lpr mice. Flow cytometry (FCM) studies also showed that Y-27632 remarkably increased Regulatory cells(Treg) cell percentage in spleen cells. Western blot analysis demonstrated Y-27632 downregulated the expressions of ROCK1, ROCK2, upregulated the expression of forkhead/winged helix transcription factor(Foxp3), and inhibited the phosphorylations of NF-κBp65 and IκBα. The findings showed that the inhibition of ROCK was beneficial for the prevention of systemic lupus erythematosus, which possibly by suppressing NF-κB activation.



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