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Recombinant human CXCL8(3‐72)K11R/G31P regulates smooth muscle cell proliferation and migration through blockage of interleukin‐8 receptor
Author(s) -
Qin YuanHua,
Fan FuShun,
Zhao Ying,
Cui Ying,
Wei XiaoQing,
Kohama Kazuhiro,
Gordon John R.,
Li Fang,
Gao Ying
Publication year - 2013
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1107
Subject(s) - mmp9 , proinflammatory cytokine , vascular smooth muscle , mmp2 , medicine , endocrinology , receptor , in vivo , cell growth , hyperlipidemia , matrix metalloproteinase , inflammation , biology , downregulation and upregulation , smooth muscle , biochemistry , microbiology and biotechnology , cancer , gene , metastasis , diabetes mellitus
Atherosclerosis is a chronic inflammatory disease with multiple contributing factors. Hyperlipidemia is one of the major independent risks, and interleukin‐8 (IL‐8), as an inflammatory factor, plays an important role in the development of atherosclerosis. The aims of the study were to examine the therapeutic efficacy of G31P, an antagonist of IL‐8 receptor, with a mouse model of hyperlipidemia and the potential mechanisms of G31P through the vascular smooth muscle cell (VSMC) proliferation and migration in a cell line. In vivo study: Male BALB/c mice were fed a high‐fat diet for 6 months. G31P was injected subcutaneously. Blood keratinocyte chemoattractant, lipid profile, and aorta expression of inflammatory factors, matrix metalloproteinases, MMP2 and MMP9 were investigated. In vitro study: A7R5 cells were treated with IL‐8 with/without G31P. Cell proliferation and migration were investigated. G31P significantly suppressed the hyperlipidermia‐induced abnormal lipid profile and increased IL‐8, proinflammatory factor, MMP2 and MMP9 expression. G31P also inhibited VSMC proliferation and migration both in vitro and in vivo . These findings indicate the potential therapeutic effects of G31P in preventing the development of atherosclerosis by antagonizing IL‐8 receptor and decreasing the biologic activity of IL‐8. © 2012 IUBMB Life, 65(1):67–75, 2013