title: Y-27632, a Rho-associated protein kinase inhibitor, inhibits systemic lupus erythematosus.
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.
authors.affiliation: Department of Histology and Embryology, Bengbu Medical college, Bengbu, 233030, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and immunology, the First Affiliated Hospital to Bengbu Medical college, Bengbu 233004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Histology and Embryology, Bengbu Medical college, Bengbu, 233030, China.
authors.forename: Jixia
authors.initials: J
authors.lastname: Chai
authors.affiliation: Department of Histology and Embryology, Bengbu Medical college, Bengbu, 233030, China.
authors.forename: Meiqun
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, Bengbu Medical college, Bengbu, 233030, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Histology and Embryology, Bengbu Medical college, Bengbu, 233030, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Pharmacology, Bengbu Medical college, Bengbu, 233030, China. Electronic address: Gemin417@sohu.com.
authors.forename: Min
authors.initials: M
authors.lastname: Ge
authors.affiliation: Department of Rheumatology and immunology, the First Affiliated Hospital to Bengbu Medical college, Bengbu 233004, China. Electronic address: uglboy2002@126.com.
authors.forename: Changhao
authors.initials: C
authors.lastname: Xie
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019463:Mice, Inbred MRL lpr; D016328:NF-kappa B / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases
keywords: Rho; Systemic lupus erythematosus; Y-27632