sauchinone and Escherichia-coli-Infections

AMP-activated protein kinase (AMPK) plays an important role in inflammation in various cells and increases the phagocytic ability of macrophages. In this study, we found that sauchinone increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in mouse peritoneal macrophages. Sauchinone increased macrophage phagocytosis of fluorescent Escherichia coli, which was blocked by compound C, an AMPK inhibitor. Sauchinone also increased the phosphorylation of p38 mitogen activated protein kinase (MAPK) in cultured macrophages in a concentration-dependent fashion, which was not blocked by compound C. However, the increase of sauchinone-induced phagocytosis was prevented by SB203580. An inhibitor of the upstream kinase TGF-beta-activated kinase (TAK1), (5z)-7-oxozeaenol, abolished the phosphorylation of ACC and p38 MAPK. Systemic administration of sauchinone to mice led to increased phosphorylation of AMPK and p38 MAPK in the lung, and enhanced phagocytosis of fluorescent E. coli in bronchoalveolar lavage fluid as compared with control mice. These results suggest sauchinone to be a useful adjunctive treatment for bacterial infection.

Topics: AMP-Activated Protein Kinases; Animals; Benzopyrans; Bronchoalveolar Lavage Fluid; Cells, Cultured; Dioxoles; Escherichia coli Infections; Escherichia coli K12; Flow Cytometry; Lignans; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Mitogen-Activated Protein Kinase Kinases; Phagocytosis; Saururaceae