nod2 downregulates tlr21 mediated il1β gene expression in mouse peritoneal macrophagesnod2会使tlr21 il1β基因表达在小鼠腹腔巨噬细胞介导的.pdfVIP

Nod2 Downregulates TLR2/1 Mediated IL1b Gene Expression in Mouse Peritoneal Macrophages Yogesh Dahiya, Rajeev Kumar Pandey, Ajit Sodhi* School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India Abstract Nod2 is a cytosolic pattern recognition receptor. It has been implicated in many inflammatory conditions. Its signaling has been suggested to modulate TLR responses in a variety of ways, yet little is known about the mechanistic details of the process. We show in this study that Nod2 knockdown mouse peritoneal macrophages secrete more IL1b than normal macrophages when stimulated with peptidoglycan (PGN). Muramyl dipeptide (MDP, a Nod2 ligand) + PGN co-stimulated macrophages have lower expression of IL1b than PGN (TLR2/1 ligand) stimulated macrophages. MDP co-stimulation have similar effects on Pam3CSK4 (synthetic TLR2/1 ligand) mediated IL1b expression suggesting that MDP mediated down regulating effects are receptor dependent and ligand independent. MDP mediated down regulation was specific for TLR2/1 signaling as MDP does not affect LPS (TLR4 ligand) or zymosan A (TLR2/6 ligand) mediated IL1b expression. Mechanistically, MDP exerts its down regulating effects by lowering PGN/Pam3CSK4 mediated nuclear cRel levels. Lower nuclear cRel level were observed to be because of enhanced transporting back rather than reduced nuclear translocation of cRel in MDP + PGN stimulated macrophages. These results demonstrate that Nod2 and TLR2/1 signaling pathways are independent and do not interact at the level of MAPK or NF-kB activation. Citation: Dahiya Y, Pandey RK, Sodhi A (2011) Nod2 Downregulates TLR2/1 Mediated IL1b Gene Expression in Mouse Peritoneal Macrophages. PLoS ONE 6(11): e27828. doi:10.1371/journal.pone.0027828 ´ Editor: Stefan Bereswill, Charite-University Medicine Ber