title: CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells.
abstract: CXCL16 is a unique chemokine with characteristics as a receptor for phosphatidylserine and oxidized low density lipoproteins in macrophages, and is involved in the accumulation of cellular cholesterol during atherosclerotic lesion development. In this study, we report a new function of CXCL16 as a novel angiogenic factor in human umbilical vein endothelial cells (HUVEC). CXCL16 stimulated proliferation and chemotaxis of HUVEC in a dose-dependent manner, reaching a maximum at 1 nM. CXCL16 also significantly induced tube formation of HUVEC on Matrigel. Further, exposure of HUVEC to CXCL16 led to a time- and dose-dependent activation of mitogen-activated protein kinase (ERK1/2), which was completely inhibited by a mitogen-activated protein kinase kinase inhibitor, PD98059. Proliferation and tube formation in response to CXCL16 were also blocked by the pretreatment with PD98059, but not CXCL16-induced chemotaxis. Thus, our data indicate that CXCL16 may act as a novel angiogenic factor for HUVEC and that ERK is involved as an important signaling molecule to mediate its angiogenic effects.
authors.affiliation: Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhuge
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murayama
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamauchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimaoka
authors.forename: Shin
authors.initials: S
authors.lastname: Yonehara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kume
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
mesh_terms: D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D014471:Umbilical Veins / Q000166:cytology*
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger