CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells.
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.
Zhuge
Xin
X
Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Murayama
Toshinori
T
Arai
Hidenori
H
Yamauchi
Ryoko
R
Tanaka
Makoto
M
Shimaoka
Takeshi
T
Yonehara
Shin
S
Kume
Noriaki
N
Yokode
Masayuki
M
Kita
Toru
T
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*
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger