NOD2 up-regulates TLR2-mediated IL-23p19 expression via NFκB subunit c-Rel in Paneth cell-like cells

作者：Tan, Gao; Liang, Erbo; Liao, Kaili; Deng, Feihong; Zhang, Wendi; Chen, Yuqing; Xu, Jun; Zhi, Fachao^*

来源：Oncotarget, 2016, 7(39): 63651-63660.

DOI：10.18632/oncotarget.11467

• interleukin-23p19
• NOD2
• Crohn's disease
• intestinal immunity

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.

• 出版日期2016-9-27
• 单位南方医科大学