点击次数：

论文类型：期刊论文

发表时间：2015-07-21

发表刊物：SCIENTIFIC REPORTS

收录刊物：SCIE、PubMed、Scopus

卷号：5

页面范围：11082

ISSN号：2045-2322

摘要：Cathelicidins are short cationic host defense peptides and play a central role in host innate immune system. Here we identified two novel cathelicidins, CI-CATH2 and 3, from Columba livia. Evolutionary analysis of avian cathelicidins via phylogenetic tree and K alpha/Ks calculations supported the positive selection that prompted evolution of CATH2 to CATH2 and 3, which originate from common ancestor and could belong to one superfamily. CI-CATH2 and 3 both adopt amphipathic et-helical comformations identified by circular dichroism and the 3D structures built by Rosetta. CI-CATH2 of CATH2 family with the most expression abundance in bird, exhibited relatively weak antimicrobial activity, but acted instead on the innate immune response without showing undesirable toxicities. In macrophages primed by LPS, CI-CATH2 significantly down-regulated the gene and protein expressions of inducible nitric oxide synthase and pro-inflammatory cytokines while enhancing the anti-inflammatory cytokine, acting through MAPK and NF-KB signaling pathways. Molecular docking shows for the first time that cathelicidin binds to the opening region of LPS-binding pocket on myeloid differentiation factor 2 (MD-2) of toll-like receptor (TLR)4-MD-2 complex, which in turn inhibits the TLR4 pathway. Our results, therefore, provide new insight into the mechanism underlying the blockade of TLR4 signaling by cathelicidins.