Dehydroepiandrosterone alleviates E. Coli 0157:H7-induced inflammation by preventing the activation of p38 MAPK and NF-κB pathways in mice peritoneal macrophages

As an important metabolite in cholesterol metabolism, dehydroepiandrosterone (DHEA) can modulate the immune function in animals and humans, but the underlying mechanism is still unclear. The present study investigated the effect and mechanism of DHEA's anti-inflammatory action in primary mice peritoneal macrophages infected with E. coli 0157:H7. The finding showed that DHEA improved the phagocytic ability in E. coli 0157:H7-infected macrophages. DHEA inhibited the cytokines (including tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) secretion in E. coli 0157:H7-infected macrophages. The inducible nitric oxide synthase and cyclooxygenase-2 protein level were significantly decreased in E. coli 0157:H7-infected macrophages treated with DHEA. In addition, DHEA markedly decreased the phospho (p)-p38 MAPK protein level in E. coli 0157:H7-infected macrophages. Furthermore, DHEA prevented the nuclear translocation of NF-kappa beta by decreasing of p-I kappa B-alpha protein level in E. coli 0157:H7-infected macrophage; and these effects of DHEA were heightened when the cells were pre-treated with p38 MAPK inhibitor SB203580. Our data indicated that DHEA alleviates the pro inflammatory mediator production in E. coli 0157:H7-infected mice peritoneal macrophages; and this beneficial action associated with it prevents the activation of p38 MAPK and NF-kappa beta signaling pathway.