NODs‐dependent OmPGRP‐L1 expression modulates the excessive inflammatory response to bacterial infection in rainbow trout liver cells (611.1)

Abstract

Peptidoglycan recognition proteins (PGRPs) recognize bacterial peptidoglycan and function in antibacterial innate immunity. OmPGRP‐L1, a long form of PGRP from the rainbow trout, is known to have an anti‐inflammatory role in liver cells. In this study, we examined the regulation of the expression of OmPGRP‐L1 in a rainbow trout hepatoma cell line RTH‐149 upon stimulation with microbial ligands. γ‐D‐glutamyl‐meso‐DAP (iE‐DAP) and muramyl dipeptide (MDP) markedly increased the expression of OmPGRP‐L1, as well as pro‐inflammatory cytokines. Silencing of nucleotide‐binding oligomerization domain‐containing protein (NOD)1 and NOD2 specifically inhibited the upregulation of OmPGRP‐L1 expression induced by their cognate ligands. Suppression of NF‐κB activation prevented the induction of OmPGRP‐L1 expression induced by iE‐DAP and MDP. In silico analysis and electrophoretic mobility shift assay revealed that the promoter of OmPGRP‐L1 had NF‐κB binding sites, suggesting that OmPGRP‐L1 is produced through NODs‐NF‐κB signaling pathway. Loss‐of‐function and gain‐of‐function experiments indicated that OmPGRP‐L1 down‐regulated the induction of pro‐inflammatory cytokine expression induced by iE‐DAP and MDP. Overall, these findings suggest that rainbow trout liver cells may modulate the excessive inflammatory response to bacterial infection by producing OmPGRP‐L1 through NODs.Grant Funding Source: Supported by the National Research Foundation of Korea (NRF‐2011‐0015180 and NRF‐2013M3A6A8073556)