Lipopolysaccharide and interleukin 1 augment the effects of hypoxia and inflammation in human pulmonary arterial tissue.
- 29 October 1996
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 93 (22) , 12478-12483
- https://doi.org/10.1073/pnas.93.22.12478
Abstract
The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor alpha on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1 beta, or tumor necrosis factor alpha augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.Keywords
This publication has 25 references indexed in Scilit:
- Induction of Interleukin 6 (IL-6) by Hypoxia in Vascular CellsJournal of Biological Chemistry, 1995
- Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide.Journal of Clinical Investigation, 1995
- Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity.Journal of Clinical Investigation, 1994
- Hypoxic induction of interleukin-8 gene expression in human endothelial cells.Journal of Clinical Investigation, 1994
- Persistence of the fetal pattern of tropoelastin gene expression in severe neonatal bovine pulmonary hypertension.Journal of Clinical Investigation, 1994
- Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia.Journal of Clinical Investigation, 1993
- Expression of Endothelin-1 in the Lungs of Patients with Pulmonary HypertensionNew England Journal of Medicine, 1993
- Intimal proliferation in an organ culture of human internal mammary arteryCardiovascular Research, 1992
- Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells.Journal of Clinical Investigation, 1990
- Interleukin 1 increases the production of endothelin-1 by cultured endothelial cellsBiochemical and Biophysical Research Communications, 1990