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

Liu,Huaizheng; Liu,Zuoliang; Zhao,Shangping; Sun,Chuanzheng; Yang,Mingshi

doi:10.3892/mmr.2015.3746

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

Authors:
- Huaizheng Liu
- Zuoliang Liu
- Shangping Zhao
- Chuanzheng Sun
- Mingshi Yang
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Affiliations: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/mmr.2015.3746
Pages: 3101-3106

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Abstract

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.

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