title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation.
abstract: Mesothelial cells are composed of monolayer of the entire surface of serosal cavities including pleural, pericardial, and peritoneal cavity. Although mesothelial cells are known to express multiple Toll-like receptors (TLRs) which contribute to trigger innate immune responses against infections, the precise molecular mechanism remains still unclear. In the present study, we investigated the role of Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF), one of the two major TLRs-adaptor molecules, on innate immune response induced by TLR3 and TLR4 stimulation in murine peritoneal mesothelial cells (PMCs). TRIF was strongly expressed in PMCs and its deficiency led to impaired production of cytokines and chemokines by poly I:C and LPS in the cells. Activation of NF-κB or MAPKs through poly I:C and LPS stimulation was reduced in TRIF-deficient PMCs as compared to the WT cells. TRIF was also necessary for optimal nitric oxide synthesis and gene expression of inducible nitric oxide synthase (iNOS) and IFN-β in PMCs in response to poly I:C and LPS. Furthermore, both Escherichia coli and Pseudomonas aeruginosa induced high level of IL-6, CXCL1, and CCL2 production in PMCs, which was significantly impaired by TRIF deficiency. These results demonstrated that TRIF is required for optimal activation of innate immune responses in mesothelial cells against microbial infections.
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Hwang
authors.affiliation: BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Tae-Hyoun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Sang-Muk
authors.initials: SM
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: School of Bioresources and Bioscience, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: jonpark@jnu.ac.kr.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D016899:Interferon-beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D011070:Poly I-C; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; C476286:Ticam1 protein, mouse
keywords: Chemokine; Mesothelial cells; Nitric oxide; TLRs; TRIF