Lipopolysaccharide and cytokines enhance bradykinin-stimulated production of PGI2 by cultured human pulmonary artery smooth muscle cells.
We have examined the bradykinin (BK)-stimulated production of prostacyclin (PGI2) by cultured human pulmonary artery smooth muscle cells (HPASMC) pretreated with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma). BK from 0.01 to 1 microM induced a dose-dependent increase in PGI2 production by HPASMC. A striking increase in PGI2 production in response to BK was observed in HPASMC which had been incubated with 1 microgram/ml LPS, 20 U/ml IL-1 beta, 50 U/ml TNF alpha or 100 U/ml IFN gamma. After incubation with various concentrations of LPS or cytokines, the production of PGI2 by BK-stimulated HPASMC showed significant, dose-dependent increases beginning at 0.1 microgram/ml of LPS, 2 U/ml of IL-1 beta and 5 U/ml of TNF alpha, while higher concentrations of IFN gamma failed to cause any further increase in PGI2 production. Our results indicate that BK is a potent agonist to stimulate HPASMC to produce PGI2. LPS, IL-1 beta and TNF alpha effectively enhanced BK-stimulated production of PGI2 by HPASMC, while IFN gamma had only a weak effect on BK-stimulated PGI2 production. Bradykinin-induced enhancement of PGI2 production by LPS, IL-1 beta and TNF alpha might be involved in the regulation of pulmonary vascular tension and prevent a paradoxical thrombogenic effect in endotoxin- or cytokine-mediated inflammation and acute lung injury. These experimental results suggest that vascular smooth muscle cells might actively control the vascular tension and blood supply by producing PGI2 in response to an agonist such as BK.
Wen
F Q
FQ
2nd Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Watanabe
K
K
Yoshida
M
M
D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008858:Microscopy, Phase-Contrast; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011464:Epoprostenol; D001920:Bradykinin