A novel anionic cathelicidin lacking direct antimicrobial activity but with potent anti-inflammatory and wound healing activities from the salamander Tylototriton kweichowensis
A novel anionic cathelicidin lacking direct antimicrobial activity but with potent anti-inflammatory and wound healing activities from the salamander Tylototriton kweichowensis
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来自贵州蝾螈的一种新型阴离子抗菌素，缺乏直接抗菌活性，但具有有效的抗炎和伤口愈合活性
DOI：
10.1016/j.biochi.2021.08.007
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发表时间：
2021-08-23
期刊：
影响因子：
3.9
通讯作者：
Wang, Yipeng
中科院分区：
文献类型：
--
作者：
Luo, Xuanjin;Ouyang, Jianhong;Wang, Yipeng
Cathelicidin是存在于脊椎动物体内的一类抗菌肽家族，在宿主对环境胁迫的应答中发挥多种功能。迄今为止鉴定的所有cathelicidin均为阳离子，未报道具有净负电荷的阴离子成员。从蝾螈皮肤中分离到一种新的阴离子抗菌肽（TK-CATH）。贵州种。与大多数其他cathelicidin成员不同，它没有表现出直接的抗菌活性。然而，它表现出很强的抗炎活性。它通过抑制LPS激活的丝裂原活化蛋白激酶（MAPK）信号通路，有效抑制LPS诱导的两栖类白细胞和小鼠巨噬细胞中促炎细胞因子基因表达和蛋白质产生。此外，TK-CATH显示出强大的伤口愈合活性。在小鼠全层皮肤创伤模型中，它能有效诱导与创伤愈合相关的多种细胞因子、趋化因子和生长因子的产生，促进角质形成细胞的运动和增殖，加速皮肤创伤愈合。这些结果表明，TK-CATH参与创伤修复过程的炎症阶段和新组织形成阶段。同时，TK-CATH具有较弱但有效的自由基清除活性和较低的细胞毒性。以上结果表明，TK-CATH是蝾螈皮肤中的一种多功能肽。贵州种。它可能在宿主抵抗细菌感染的免疫应答和皮肤创伤修复中发挥重要作用。(c)2021 Elsevier B.V.和Societe Francaise de Biochimie et Biologie Moleculaire（SFBBM）。All rights reserved.
Cathelicidin is a family of antimicrobial peptides (AMPs) existing in vertebrates, which play multiple functions in host responses against environmental stresses. All cathelicidins identified to date are cationic, no anionic member with net negative charges has been reported. In the present study, a novel anionic cathelicidin (TK-CATH) with a net charge of-3 was identified from the skin of the salamander, T. kweichowensis. Unlike most other cathelicidin members, it didn't exhibit direct antimicrobial activity. However, it demonstrated strong anti-inflammatory activity. It effectively inhibited the LPS-induced pro inflammatory cytokine gene expression and protein production in amphibian leukocytes and mouse macrophages by inhibiting the LPS-activated mitogen-activated protein kinase (MAPK) signaling pathways. Besides, TK-CATH showed potent wound healing activity. It could effectively induce the production of several cytokines, chemokines and growth factors relating to wound healing, promote the motility and proliferation of keratinocytes, and accelerate the skin wound healing in a mouse full-thickness wound model. These results imply that TK-CATH participates in both the inflammatory phase and new tissue formation phase of wound repair process. Meanwhile, TK-CATH exhibited weak but effective free radical scavenging activity and low cytotoxicity. All the results above indicate that TK-CATH is a multifunctional peptide in the skin of the salamander T. kweichowensis. It may play important roles in host immune responses against bacterial infection and skin wound repair. (c) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.