Role of AMP-activated protein kinase in regulating LPS-induced secretion of inflammatory cytokines in mouse alveolar macrophages

Abstract

Objective To investigate the mechanism of 5' adenosine monophosphate-activated protein kinase (AMPK) in the regulation of LPS-induced secretion of inflammatory cytokines in mouse alveolar macrophages. Methods Alveolar macrophages were isolated from wild type and AMPKα1-/- C57BL/6J mice. ELISA was used to measure the concentrations of IL-1β and TNF-α in the culture supernatants of LPS treated alveolar macrophages with or without 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) stimulation. Western blot assay was performed to analyze the expression of AMPKα1 and AMPKα2 in alveolar macrophages isolated from wild type and AMPKα1-/- mice as well as the LPS-induced changes of p-AMPKα activity in wild type mice. Results The LPS-induced secretion of inflammatory cytokines in alveolar macrophages isolated from AMPKα1-/- mice were significantly higher than that of wild type mice. The activities of p-AMPKα in wild type mice were suppressed by LPS treatment. Treatment of AICAR inhibited the LPS-induced secretion of TNF-α and IL-1β. Conclusion The LPS-induced secretion of inflammatory cytokines was enhanced in AMPKα1-deficient mice, but could be suppressed upon the treatment of AICAR, an agonist of AMPK. AMPK was involved in the regulation of LPS-induced secretion of inflammatory cytokines by alveolar macrophages in mice. Key words: Mice alveolar macrophage; Adenosine monophosphate-activated protein kinase; LPS; Inflammatory cytokine