Wu Jiena, Zhang Haiyun, Chen Xiaoxin, Chai Jinwei, Hu Yunrui, Xiong Weichen, Lu Wancheng, Tian Maolin, Chen Xin, 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 Aug 16;12:731056. doi: 10.3389/fphar.2021.731056. eCollection 2021.
Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of FM-CATH was found to adopt an amphipathic α-helix structural in membrane-mimetic environments and possess favorable antimicrobial effects against bacteria and fungus. In addition, it triggered the agglutination of bacteria. It could also strongly bind to LPS and LTA. Additionally, FM-CATH affected the enzymatic activities of thrombin, plasmin, β-tryptase, and tPA, leading to coagulation inhibition and . Finally, we observed that FM-CATH improved survival rate and inhibited pathological alteration, bacterial count, serum biochemistry, and pro-inflammatory cytokine expression in the cecal ligation and puncture-induced sepsis mice. Taken together, these findings suggest that FM-CATH might be served as a promising agent for the treatment of sepsis.
脓毒症是由严重感染引起的一种加剧的炎症反应。作为天然免疫中的重要防御分子,据报道几种抗菌肽可预防脓毒性休克。在本研究中,我们从青蛙皮肤中鉴定出一种新型的cathelicidin,即FM-CATH。发现FM-CATH在模拟膜环境中呈两亲性α-螺旋结构,对细菌和真菌具有良好的抗菌作用。此外,它可引发细菌凝集。它还能与脂多糖(LPS)和脂磷壁酸(LTA)强烈结合。此外,FM-CATH影响凝血酶、纤溶酶、β-组织蛋白酶G和组织型纤溶酶原激活剂(tPA)的酶活性,导致凝血抑制。最后,我们观察到FM-CATH提高了盲肠结扎和穿刺诱导的脓毒症小鼠的存活率,并抑制了其病理改变、细菌计数、血清生化指标和促炎细胞因子表达。综上所述,这些发现表明FM-CATH可能是一种有前途的脓毒症治疗药物。