Tian Maolin, Liu Junfang, Chai Jinwei, Wu Jiena, Xu Xueqing
Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Front Pharmacol. 2021 Dec 16;12:783108. doi: 10.3389/fphar.2021.783108. eCollection 2021.
Brevinins are an important antimicrobial peptide (AMP) family identified in the skin of frogs and generally contain a characteristic ranabox structure at their C-terminal sequence. Herein a novel AMP named brevinin-2MP has been identified from the skin of the frog by molecular cloning. Brevinin-2MP (GVITDTLKGVAKTVAAELLRKAHCKLTNSC) with a high amphipathic α-helix in sodium dodecyl sulfate solutions can destroy bacterial cell membrane and kill microbes. Furthermore, brevinin-2MP has been found to inhibit the lipopolysaccharide (LPS)-induced expression of pro-inflammatory NO, MCP-1, IL-6, and TNF-α binding unidentified targets on the cell membrane and consequently suppressing the activation of MAPK/NF-κB signaling cascades induced by LPS in RAW 264.7 cells. Consistently, brevinin-2MP significantly alleviates the acute inflammatory response in carrageenan-induced mice paw. In conclusion, brevinin-2MP with anti-inflammatory and antimicrobial properties will be an ideal candidate drug molecule for bacterial inflammation treatment.
铃蟾肽是在青蛙皮肤中发现的一种重要抗菌肽(AMP)家族,其C端序列通常含有特征性的蛙皮素盒结构。在此,通过分子克隆从青蛙皮肤中鉴定出一种名为铃蟾肽-2MP的新型AMP。铃蟾肽-2MP(GVITDTLKGVAKTVAAELLRKAHCKLTNSC)在十二烷基硫酸钠溶液中具有高度两亲性α螺旋,可破坏细菌细胞膜并杀死微生物。此外,已发现铃蟾肽-2MP抑制脂多糖(LPS)诱导的促炎NO、MCP-1、IL-6和TNF-α的表达,其通过结合细胞膜上未明确的靶点,从而抑制RAW 264.7细胞中LPS诱导的MAPK/NF-κB信号级联的激活。同样,铃蟾肽-2MP显著减轻角叉菜胶诱导的小鼠爪中的急性炎症反应。总之,具有抗炎和抗菌特性的铃蟾肽-2MP将是治疗细菌炎症的理想候选药物分子。