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Human airway smooth muscle cells secrete vascular endothelial growth factor: up‐regulation by bradykinin via a protein kinase C and prostanoid‐dependent mechanism
Author(s) -
KNOX ALAN J.,
CORBETT LISA,
STOCKS JOANNE,
HOLLAND ELAINE,
ZHU YONG M.,
PANG LINHUA
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0256com
Subject(s) - bradykinin , angiogenesis , vascular endothelial growth factor , secretion , proinflammatory cytokine , vascular smooth muscle , vascular endothelial growth factor a , endocrinology , medicine , vascular endothelial growth factor b , microbiology and biotechnology , biology , cancer research , inflammation , receptor , vegf receptors , smooth muscle
Bronchial vascular remodeling is an important feature of the pathology of chronic asthma, but the responsible mechanisms and main sources of an‐giogenic factors are unclear. Here we report that human airway smooth muscle cells express vascular endo‐thelial growth factor (VEGF) 121,165,189,206 splice variants and secrete VEGF protein constitutively. VEGF protein secretion was increased by the proinflammatory asthma mediator bradykinin through post‐transcrip‐tional mechanisms. Bradykinin‐induced VEGF secretion was dependent on the B 2 bradykinin receptor activation of protein kinase C and generation of endogenous prostanoids. This is the first report that bradykinin can increase VEGF secretion in any biological system and the first to show that airway smooth muscle cells produce VEGF. Our results suggest a novel role for human airway smooth muscle in contributing to bronchial mucosal angiogenesis in chronic asthma by secretion of VEGF and suggest a wider role for mesen‐chymal cell products in mediating angiogenesis in inflammatory and allergic diseases.—Knox, A. J., Corbett, L., Stocks, J., Holland, E., Zhu, Y. M., Pang, L. Human airway smooth muscle cells secrete vascular endothelial growth factor: up‐regulation by bradykinin via a protein kinase C and prostanoid‐dependent mechanism. FASEB J . 15, 2480–2488 (2001)