title: NOD2 up-regulates TLR2-mediated IL-23p19 expression via NF-κB subunit c-Rel in Paneth cell-like cells.
abstract: IL-23p19 plays important roles in intestinal antimicrobial immunity, while its over-expression can lead to intestinal inflammation. However, the bacterial compounds and the type of pattern recognition receptor involved in the inducible expression of IL-23p19 in Paneth cells remain unclear. Here we show that the mRNA expression of IL-23p19 was increased in Paneth cell (PC)-like cells stimulated by Toll-like receptor 2 (TLR2) ligands, peptidoglycan (PGN) and Pam3CSK4, and was further increased in the presence of nucleotide-binding oligomerization domain 2 (NOD2)-ligand muramyl dipeptide (MDP). However, its mRNA expression was decreased in NOD2-knockdown PC-like cells. Additionally, the c-Rel activation was increased in Pam3CSK4- or PGN-stimulated PC-like cells, but the PGN-induced c-Rel activation was decreased in NOD2-knockdown PC-like cells and had no significant difference compared with Pam3CSK4-induced c-Rel activation. Our results suggest that NOD2 up-regulates TLR2-mediated IL-23p19 expression via increasing c-Rel activation in PC-like cells. This finding might provide us with a novel therapeutic target for inflammatory bowel disease to inhibit IL-23p19 over-expression via the NOD2-c-Rel pathway.
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Gao
authors: G
authors: Tan
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Erbo
authors: E
authors: Liang
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Kaili
authors: K
authors: Liao
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Feihong
authors: F
authors: Deng
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Wendi
authors: W
authors: Zhang
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Yuqing
authors: Y
authors: Chen
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Jun
authors: J
authors: Xu
authors: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Fachao
authors: F
authors: Zhi
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism*; D007422:Intestines / Q000276:immunology; D008024:Ligands; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D019879:Paneth Cells / Q000166:cytology*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: C508840:IL23A protein, human; D053760:Interleukin-23 Subunit p19; D008024:Ligands; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D020569:Proto-Oncogene Proteins c-rel; C068059:REL protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
keywords: Crohn's disease; NOD2; interleukin-23p19; intestinal immunity