Both Prostaglandin E2 and Nitric Oxide Sequentially Mediate the Tumor Necrosis Factor α–Induced Inhibition of Surfactant Synthesis by Human Type II Pneumocytes

Abstract

The NO generation, secondary to PGE2 production, seems responsible for the TNF-alpha-induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes. Nitric oxide seems to exert this effect through activation of guanylyl cyclase.

Carbon Monoxide Contributes to the Cytokine-Induced Inhibition of Surfactant Synthesis by Human Type II Pneumocytes

“…We have previously shown that NO generation participated in the TNF-a-induced inhibition of phosphatidylcholine syn¬ thesis by type II pneumocytes of human origin and that NO exerted this effect through the stimufation of gua¬ nylyl cyclase and cGMP accumulation. 5 The results of our study further confirm those findings. When we cul¬ tured pneumocytes in the presence of NO synthase in¬ hibitors, however, the cytokine-induced cGMP accumu¬ lation and subsequent effect on phosphatidylcholine synthesis were not completely prevented, suggesting that other molecules capable of stimulating guanylyl cyclase are being simultaneously induced by cytokines.…”

The Physiology and Pathophysiology of Nitric Oxide in the Lung

“…Additional deleterious consequences of iNOS induction include suppression of sodium transport in pulmonary epithelial cells [136] and of surfactant synthesis in type II pneumocytes [13 7]. The latter effect appears to be mediated by cyclic GMP [137]. In addition, iNOS expression by TNF-a in tracheal epithelial cells has been proposed to cause mucin hypersecretion [4].…”