Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation

•TRIF is involved in cytokines and chemokines production by poly I:C and LPS in PMCs.•TRIF mediates iNOS expression and NO production by poly I:C or LPS in PMCs.•TRIF is required for IFN-β gene expression in PMCs stimulated by poly I:C or LPS.•TRIF is essential for optimal production of IL-6, CXCL1,...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 2016-01, Vol.77, p.127-134
Main Authors: Hwang, Eun-Ha, Kim, Tae-Hyoun, Oh, Sang-Muk, Lee, Kyung-Bok, Yang, Soo-Jin, Park, Jong-Hwan
Format: Article
Language:English
Subjects:
Adaptor Proteins, Vesicular Transport - genetics
Adaptor Proteins, Vesicular Transport - metabolism
Animals
Blotting, Western
Cells, Cultured
Chemokine
Chemokine CCL2 - metabolism
Chemokine CXCL1 - metabolism
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - microbiology
Escherichia coli - physiology
Gene Expression - drug effects
Immunity, Innate - genetics
Immunity, Innate - immunology
Interferon-beta - genetics
Interferon-beta - metabolism
Interleukin-6 - metabolism
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Macrophages - metabolism
Mesothelial cells
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinases - metabolism
NF-kappa B - metabolism
Nitric oxide
Nitric Oxide Synthase Type II - genetics
Nitric Oxide Synthase Type II - metabolism
Peritoneum - cytology
Peritoneum - metabolism
Poly I-C - pharmacology
Pseudomonas aeruginosa - physiology
Reverse Transcriptase Polymerase Chain Reaction
TLRs
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - metabolism
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - metabolism
TRIF
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Summary:•TRIF is involved in cytokines and chemokines production by poly I:C and LPS in PMCs.•TRIF mediates iNOS expression and NO production by poly I:C or LPS in PMCs.•TRIF is required for IFN-β gene expression in PMCs stimulated by poly I:C or LPS.•TRIF is essential for optimal production of IL-6, CXCL1, and CCL2 by live G-bacteria. 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.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2015.11.010