Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6286231 | Neuroscience Research | 2014 | 9 Pages |
Abstract
Toll-like receptor (TLR) 3 is a pattern recognition receptor that recognizes double-stranded RNA (dsRNA). TLR3 signaling in astrocytes leads to the expression of interferon-β (IFN-β), and IFN-β regulates immune and inflammatory reactions by inducing IFN-stimulated genes (ISGs). We demonstrated in the present study that polyinosinic-polycytidylic acid (poly IC), an authentic dsRNA, up-regulated the expression of ISG54 and ISG56 in U373MG human astrocytoma cells. This reaction was confirmed to be mediated via the TLR3/IFN-β pathway. We also found that ISG56 positively regulates the expression of ISG54, retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). In addition, positive feedback loops were found between ISG54 and ISG56, and also between ISG54 and RIG-I. RNA interference experiments revealed that all of ISG54, ISG56, RIG-I and MDA5 were involved in the poly IC-induced expression of a chemokine CXCL10. These results suggest that ISG54 and ISG56 are involved in the induction of CXCL10 in TLR3/IFN-β signaling at least partly by co-operating with RIG-I and MDA5. ISG54 and ISG56 may contribute to immune and inflammatory reactions elicited by the TLR3/IFN-β signaling pathway in astrocytes, and may play an important role both in antiviral immunity and in neuroinflammatory diseases.
Keywords
PAMPsISG56CXCL10MDA5ISGRIG-IPRRsTLR3TLRIFN-βDAMPsdanger-associated molecular patternspathogen-associated molecular patternsinterferonIFNToll-like receptorPoly ICpolyinosinic-polycytidylic acidmelanoma differentiation-associated gene 5retinoic acid-inducible gene-Iinterferon-stimulated genepattern recognition receptors
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Authors
Tadaatsu Imaizumi, Akiko Numata, Chikashi Yano, Hidemi Yoshida, Pengfei Meng, Ryo Hayakari, Fei Xing, Lian Wang, Tomoh Matsumiya, Kunikazu Tanji, Tetsuya Tatsuta, Manabu Murakami, Hiroshi Tanaka,