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

• Published in: Molecular medicine reports Vol. 12; no. 2; pp. 3101 - 3106
• Main Authors: LIU, HUAIZHENG, LIU, ZUOLIANG, ZHAO, SHANGPING, SUN, CHUANZHENG, YANG, MINGSHI
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-08-2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Abdomen; Agonists (Biochemistry); Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Apoptosis; BML-111; Caspase; Caspase 3 - genetics; Caspase 3 - immunology; Caspase-3; Cecum; Cytokines; Defensins - agonists; Defensins - genetics; Defensins - immunology; Disease Models, Animal; Drug therapy; Gene expression; Gene Expression Regulation; Health aspects; Hemorrhage; Heptanoic Acids - pharmacology; Humans; Immune response; Immunity, Mucosal - drug effects; Inflammation; Injections, Intraperitoneal; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - immunology; Intestinal mucosa; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; intestinal mucosal barrier; Intestine; Kinases; Laboratory animals; Lipoxin A4; Male; Molecular modelling; Mucosa; Physiological aspects; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Sepsis; Sepsis - drug therapy; Sepsis - genetics; Sepsis - immunology; Sepsis - pathology; Signal Transduction; Small intestine; Studies; TLR2; TLR4 protein; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-like receptors; Transforming growth factor; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - immunology; Transforming growth factor-b; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; China; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2015.3746

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.