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Immunol Cell Biol. 2016 Oct;94(9):875-885. doi: 10.1038/icb.2016.57. Epub 2016 Jun 17.

Polyinosinic-polycytidylic acid inhibits the differentiation of mouse preadipocytes through pattern recognition receptor-mediated secretion of tumor necrosis factor-α.

Yu L1,2, Liu G1,2, Yang C1,2, Song X1,2, Wang H2.

Author information

1
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province, China.
2
Research Center for Immunology, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.

Abstract

Viral infections can disturb the functions of adipose tissues and thus result in metabolic diseases. Polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of viral double-stranded RNA, induces innate antiviral responses by mimicking viral infection through the activation of pattern recognition receptors (PRRs) such as Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Poly(I:C) also inhibits the differentiation of mouse preadipocytes but the mechanism underlying this process remains unclear. In this study, poly(I:C) inhibited preadipocyte differentiation in a dose-dependent manner, but not in a time-dependent manner. Endogenously transfected poly(I:C) severely impaired the adipogenesis of preadipocytes compared with exogenously added poly(I:C). Low concentration of tumor necrosis factor-α (TNF-α) could effectively inhibit the preadipocyte differentiation. The effect of exogenously added poly(I:C) on inhibition of differentiation was significantly diminished in the preadipocytes of TLR3 knockout mice. By contrast, endogenously transfected poly(I:C) still inhibited the differentiation of TLR3-deficient preadipocytes. Hence, MDA5/RIG-I signaling was involved in the poly(I:C)-induced inhibition of preadipocyte differentiation. The effect of poly(I:C) stimulation, either through endogenous transfection or exogenous addition, on inhibition of differentiation was significantly diminished in the preadipocytes of TNF-α knockout mice. These results confirmed the evidence that poly(I:C) inhibited the differentiation of mouse preadipocytes through PRR-mediated secretion of TNF-α.

PMID:
27311810
DOI:
10.1038/icb.2016.57
[Indexed for MEDLINE]

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