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Effect of BML111 on the intestinal mucosal barrier in sepsis and its mechanism of action

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5(S),6(R)7trihydroxymethyl heptanoate (BML111) is an lipoxin A4 receptor agonist, which modulates the immune response and attenuates hemorrhagic shockinduced acute lung injury. However, the role of BML111 in sepsis and in the intestinal mucosal barrier are not well understood. Therefore, the present study was designed to investigate the effect of BML111 on the intestinal mucosal barrier in a rat model of sepsis. Furthermore, the molecular mechanism of action of BML111 was evaluated. The cecal ligation and puncture-induced rat model of sepsis was constructed, and BML111 was administered at three different doses. The results revealed that BML111 suppressed the elevation of the proinflammatory cytokines tumor necrosis factorα and interleukin6, while enhancing the elevation of the antiinflammatory cytokine transforming growth factorβ in the intestine. In addition, BML111 significantly upregulated rat defensin5 mRNA expression levels and downregulated the induction of cell apoptosis as well as caspase3 activity in the intestine. All these results demonstrated that BML111 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 BML111. The present study therefore suggested that BML-111 may be a novel therapeutic agent for sepsis.
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Document Type: Research Article

Affiliations: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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