title: Antimicrobial peptide Cathelicidin-BF prevents intestinal barrier dysfunction in a mouse model of endotoxemia.
abstract: Intestinal barrier functions are altered during the development of sepsis. Cathelicidin antimicrobial peptides, such as LL-37 and mCRAMP, can protect animals against intestinal barrier dysfunction. Cathelicidin-BF (C-BF), a new cathelicidin peptide purified from the venom of the snake Bungarus fasciatus, has been shown to have both antimicrobial and anti-inflammatory properties. This study investigated whether C-BF pretreatment could protect the intestinal barrier against dysfunction in a mouse model of endotoxemia, induced by intraperitoneal injection of LPS (10mg/kg). Mice were treated with low or high dose C-BF before treatment with LPS, and samples were collected 5h after LPS treatment. C-BF reduced LPS induced intestinal histological damage and gut permeability to 4 KD Fluorescein-isothiocyanate-conjugated dextran. Pretreatment with C-BF prevented LPS induced intestinal tight junction disruption and epithelial cell apoptosis. Moreover, C-BF down regulated the expression and secretion of TNF-α, a process involving the NF-κB signaling pathway. C-BF also reduced LPS induced TNF-α expression through the NF-κB signaling pathway in mouse RAW 264.7 macrophages. These findings indicate that C-BF can prevent gut barrier dysfunction induced by LPS, suggesting that C-BF may be used to develop a prophylactic agent for intestinal injury in endotoxemia.
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China.
authors: Deguang
authors: D
authors: Song
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China.
authors: Xin
authors: X
authors: Zong
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China.
authors: Haiwen
authors: H
authors: Zhang
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China.
authors: Tenghao
authors: T
authors: Wang
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China.
authors: Hongbo
authors: H
authors: Yi
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China.
authors: Chao
authors: C
authors: Luan
authors: National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Key laboratory of Molecular Animal Nutrition, Ministry of Education, Institute of Feed Science, Zhejiang University, Hangzhou, China. Electronic address: yzwang@zju.edu.cn.
authors: Yizhen
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017838:Bungarus / Q000276:immunology*; D054804:Cathelicidins / Q000008:administration & dosage* / Q000302:isolation & purification; D002460:Cell Line; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012910:Snake Venoms / Q000008:administration & dosage* / Q000302:isolation & purification; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054804:Cathelicidins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012910:Snake Venoms; D014409:Tumor Necrosis Factor-alpha
keywords: Antimicrobial peptide; Apoptosis; Intestinal permeability; NF-κB; Tight junction