Effect of BML-111 on the intestinal mucosal barrier in sepsis and its mechanism of action.

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5(S),6(R)-7-trihydroxymethyl heptanoate (BML-111) is an lipoxin A4 receptor agonist, which modulates the immune response and attenuates hemorrhagic shock-induced acute lung injury. However, the role of BML-111 in sepsis and in the intestinal mucosal barrier are not well understood. Therefore, the present study was designed to investigate the effect of BML-111 on the intestinal mucosal barrier in a rat model of sepsis. Furthermore, the molecular mechanism of action of BML-111 was evaluated. The cecal ligation and puncture-induced rat model of sepsis was constructed, and BML-111 was administered at three different doses. The results revealed that BML-111 suppressed the elevation of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6, while enhancing the elevation of the anti-inflammatory cytokine transforming growth factor-β in the intestine. In addition, BML-111 significantly upregulated rat defensin-5 mRNA expression levels and downregulated the induction of cell apoptosis as well as caspase-3 activity in the intestine. All these results demonstrated that BML-111 exerted protective effects on the intestinal mucosal barrier in sepsis. Further, it was indicated that alterations in the expression of toll-like receptor (TLR)2 and TLR4 may be one of the molecular mechanisms underlying the protective effect of BML-111. The present study therefore suggested that BML-111 may be a novel therapeutic agent for sepsis.