Interleukin-8. A mitogen and chemoattractant for vascular smooth muscle cells.
Interleukin-8 (IL-8) is a chemokine produced by a variety of cell types involved in atherogenesis and is chemotactic for neutrophils and lymphocytes. A recent study has shown that IL-8 is angiogenic and induces proliferation and chemotaxis of endothelial cells. The present study was undertaken to find out whether IL-8 is also mitogenic and chemotactic for vascular smooth muscle cells. IL-8 induced a concentration-dependent (0.1 to 10 nmol/L) stimulation of DNA synthesis and cell proliferation in both human and rat aortic smooth muscle cells. In addition, IL-8 stimulated smooth muscle cells to produce prostaglandin E2, which can inhibit IL-8-induced smooth muscle cell proliferation. In the presence of indomethacin (5 mumol/L), IL-8 (1 nmol/L) stimulated an increase in human and rat aortic smooth muscle cell number during a 3-day period of incubation by 61 +/- 16% and 59 +/- 7% (n = 4), respectively. IL-8 also increased DNA synthesis in human and rat aortic smooth muscle cells by 98 +/- 10% and 151 +/- 27% (n = 5), respectively. Moreover, IL-8 stimulated rat aortic smooth muscle cell migration by 20-fold over the control value, with an EC50 value of 0.83 nmol/L; this chemotactic activity of IL-8 was also potentiated by indomethacin. Exposure of smooth muscle cells to IL-8 caused rapid and transient expression of the immediate-early genes c-fos and zif268 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Cardiovascular Pharmacology, Smith-Kline Beecham Pharmaceuticals, King of Prussia, Pa. 19406-0939.
T L
TL
Yue
X
X
Wang
C P
CP
Sung
B
B
Olson
P J
PJ
McKenna
J L
JL
Gu
G Z
GZ
Feuerstein
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D017781:Genes, Immediate-Early; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002630:Chemotactic Factors; D016209:Interleukin-8; D008934:Mitogens; D012333:RNA, Messenger; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases