Dehydroepiandrosterone alleviates E. Coli O157:H7-induced inflammation by preventing the activation of p38 MAPK and NF-κB pathways in mice peritoneal macrophages

Abstract

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 O157:H7. The finding showed that DHEA improved the phagocytic ability in E. coli O157:H7-infected macrophages. DHEA inhibited the cytokines (including tumor necrosis factor-α, interleukin-1β and interleukin-6) secretion in E. coli O157:H7-infected macrophages. The inducible nitric oxide synthase and cyclooxygenase-2 protein level were significantly decreased in E. coli O157:H7-infected macrophages treated with DHEA. In addition, DHEA markedly decreased the phospho (p)-p38 MAPK protein level in E. coli O157:H7-infected macrophages. Furthermore, DHEA prevented the nuclear translocation of NF-κB by decreasing of p-IκB-α protein level in E. coli O157: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 O157:H7-infected mice peritoneal macrophages; and this beneficial action associated with it prevents the activation of p38 MAPK and NF-κB signaling pathway.