title: Recombinant human CXCL8(3-72)K11R/G31P regulates smooth muscle cell proliferation and migration through blockage of interleukin-8 receptor.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, China.
authors.forename: YuanHua
authors.initials: Y
authors.lastname: Qin
authors.forename: FuShun
authors.initials: F
authors.lastname: Fan
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: XiaoQing
authors.initials: X
authors.lastname: Wei
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kohama
authors.forename: John R
authors.initials: JR
authors.lastname: Gordon
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D017931:DNA Primers; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000166:cytology*; D016133:Polymerase Chain Reaction; D053700:Receptors, Interleukin-8 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D016209:Interleukin-8; D053700:Receptors, Interleukin-8; D011994:Recombinant Proteins