title: Regulation of human enteric α-defensins by NOD2 in the Paneth cell lineage.
abstract: Human enteric α-defensins (HD5 and HD6), major antimicrobial peptides produced by Paneth cells in the intestine, play important roles in intestinal innate immunity. Since their expression is decreased in Crohn's disease (CD), with decreased expression being more pronounced in the presence of NOD2 mutations, it would be extremely interesting to investigate the mechanism by which NOD2 may regulate expression of human enteric α-defensins. Here we show that although NOD2 by itself can slightly up-regulate expression of enteric α-defensins mainly through activation of the NF-κB pathway, it can strongly down-regulates their expression during differentiation of the Paneth cell lineage mainly by inhibiting activation of the MAPK pathway. Since NOD2 is over-expressed in CD and mutant NOD2 cannot result in NF-κB activity, our finding can provide an explanation of the previous observation showing decreased expression of human enteric α-defensin in CD and even more so in the presence of NOD2 mutations. In addition, this finding provides a new view on the function of NOD2 in regulating intestinal innate immunity.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of South China University, Hengyang 421001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: zhifc41532@163.com.
authors.forename: Fa-Chao
authors.initials: FC
authors.lastname: Zhi
mesh_terms: D018938:Caco-2 Cells; D019070:Cell Lineage; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019879:Paneth Cells / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D023084:alpha-Defensins / Q000096:biosynthesis* / Q000276:immunology
chemical_list: C500225:DEFA5 protein, human; C517765:DEFA6 protein, human; D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D023084:alpha-Defensins; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Crohn's disease; Human enteric α-defensins; Intestinal innate immunity; NOD2