title: Effect of BML-111 on the intestinal mucosal barrier in sepsis and its mechanism of action.
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.
authors.affiliation: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Huaizheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Zuoliang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Shangping
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Chuanzheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Emergency and Intensive Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D023082:Defensins / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D000894:Anti-Inflammatory Agents, Non-Steroidal; D023082:Defensins; D006538:Heptanoic Acids; D015850:Interleukin-6; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3