LIPOPOLYSACCHARIDE AND INTERLEUKIN-1 AUGMENT THE EFFECTS OF HYPOXIA AND INFLAMMATION IN HUMAN PULMONARY ARTERIAL TISSUE

The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor a! on the expression of genes encoding endot helial 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 cultur es, Hypoxia decreased the expression of constitutive endothelial nitri c oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normo xic conditions, The inhibition of expression of NOS-3 corresponded wit h 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 t he inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8, Here, we have shown that inflammato ry mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in hum an pulmonary endothelial cells and whole pulmonary artery organoid cul tures.