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

  • Biomed Pharmacother. 2017 Apr:88:359-366. doi: 10.1016/j.biopha.2017.01.069.
Yuanyuan Wang  1 ,  Yang Lu  2 ,  Jixia Chai  1 ,  Meiqun Sun  1 ,  Xiaodong Hu  1 ,  Wenxin He  1 ,  Min Ge  3 ,  Changhao Xie  4
Affiliations
  • 1. Department of Histology and Embryology, Bengbu Medical college, Bengbu, 233030, China.
  • 2. Department of Rheumatology and immunology, the First Affiliated Hospital to Bengbu Medical college, Bengbu 233004, China.
  • 3. Department of Pharmacology, Bengbu Medical college, Bengbu, 233030, China. Electronic address: [email protected].
  • 4. Department of Rheumatology and immunology, the First Affiliated Hospital to Bengbu Medical college, Bengbu 233004, China. Electronic address: [email protected].
PMID: 28122300 DOI: 10.1016/j.biopha.2017.01.069
Abstract

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.

Keywords
Rho; Systemic lupus erythematosus; Y-27632.
Products