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.

Cathelicidin 是一种存在于脊椎动物中的抗菌肽 (AMP) 家族，在宿主对环境压力的反应中发挥多种功能。迄今为止鉴定的所有cathelicidins 都是阳离子的，没有报告带有净负电荷的阴离子成员。在本研究中，从蝾螈T. kweichowensis的皮肤中鉴定出一种净电荷为 -3 的新型阴离子导管素 (TK-CATH). 与大多数其他导管素成员不同，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 诱导的两栖动物白细胞和小鼠巨噬细胞中的促炎细胞因子基因表达和蛋白质产生。此外，TK-CATH 表现出强大的伤口愈合活性。在小鼠全层创面模型中，它可以有效诱导多种与创面愈合相关的细胞因子、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，加速皮肤创面愈合。这些结果表明TK-CATH参与了伤口修复过程的炎症阶段和新组织形成阶段。同时，TK-CATH 表现出较弱但有效的自由基清除活性和低细胞毒性。以上所有结果表明TK-CATH是蝾螈皮肤中的多功能肽贵州毛茛。它可能在宿主针对细菌感染的免疫反应和皮肤伤口修复中发挥重要作用。