title: PGRP negatively regulates NOD-mediated cytokine production in rainbow trout liver cells.
abstract: Pattern-recognition receptors (PRRs) initiate innate immunity via pathogen recognition. Recent studies suggest that signalling pathways downstream of different PRRs and their crosstalk effectively control immune responses. However, the cross-regulation among PRRs and its effects have yet to be fully described in fish. Here, we examined the crosstalk between OmPGRP-L1, a long form of PGRP in rainbow trout, and other PRRs during pathogenic infections. OmPGRP-L1 expression was increased in RTH-149 cells by iE-DAP and MDP, which are agonists of NOD1 and NOD2, respectively. The silencing of NOD1 and NOD2 specifically inhibited the upregulation of OmPGRP-L1 expression induced by their cognate ligands. Suppression of RIP2 and NF-κB activation prevented the induction of OmPGRP-L1 expression. An in silico analysis and electrophoretic mobility shift assay revealed that the promoter of OmPGRP-L1 has NF-κB binding sites, suggesting that OmPGRP-L1 is produced through the NOD-RIP2-NF-κB signalling pathway. Loss-of-function and gain-of-function experiments indicated that OmPGRP-L1 downregulates the induction of NOD-mediated pro-inflammatory cytokine expression. Mechanistically, secreted OmPGRP-L1 inhibited the activation of the NOD-induced NF-κB pathway via downregulation of TAK1 and IκBα phosphorylation through A20 expression. Our data demonstrate that OmPGRP-L1 and NODs might play interdependent roles in the inflammatory response to bacterial infections in rainbow trout.
authors.affiliation: Research Institute of Life Science, Gyeongsang National University, Jinju 52828, South Korea.
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Division of Life Science, Gyeongsang National University, Jinju 52828, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Life Science, Gyeongsang National University, Jinju 52828, South Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Jang
authors.affiliation: Research Institute of Life Science, Gyeongsang National University, Jinju 52828, South Korea.|Division of Life Science, Gyeongsang National University, Jinju 52828, South Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D022781:Hepatocytes / Q000276:immunology*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D017686:Oncorhynchus mykiss; D010457:Peptidoglycan / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein