Acute hypoxia decreases E. coli LPS-induced cytokine production and NF-kappa B activation in alveolar macrophages

作者：Matuschak George M^*; Nayak Ravi; Doyle Timothy M; Lechner Andrew J

来源：Respiratory Physiology & Neurobiology, 2010, 172(1-2): 63-71.

DOI：10.1016/j.resp.2010.05.006

• Gram-negative bacterial sepsis
• Lung hypoxia/reoxygenation
• Hypoxic threshold
• Rat alveolar macrophages
• Systems biology

Reductions in alveolar oxygenation during lung hypoxia/reoxygenation (H/R) injury are common after gram-negative endotoxemia. However, the effects of H/R on endotoxin-stimulated cytokine production by alveolar macrophages are unclear and may depend upon thresholds for hypoxic oxyradical generation in situ. Here INF-alpha. and IL-1 beta production were determined in rat alveolar macrophages stimulated with Escherichia coli lipopolysaccharide (LPS, serotype O55:B5) while exposed to either normoxia for up to 24 h, to brief normocarbic hypoxia (1.5 h at an atmospheric PO(2) = 10 +/- 2 mm Hg), or to combined H/R. LPS-induced TNE-alpha and IL-1 beta were reduced at the peak of hypoxia and by reoxygenation in LPS + H/R cells (P < 0.01) compared with normoxic controls despite no changes in reduced glutathione (GSH) or in PGE2 production. Both TNF-alpha mRNA and NF-kappa B activation were reduced by hypoxia that suppressed superoxide anion generation. Thus, dynamic reductions in the ambient PO(2) of alveolar macrophages that do not deplete GSH suppress LPS-induced TNF-alpha expression, IL-1 beta production, and NF-kappa B activation even as oxyradical production is decreased.

• 出版日期2010-6-30