Journal
NEUROSCIENCE RESEARCH
Volume 76, Issue 4, Pages 195-206Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neures.2013.05.002
Keywords
TLR4; MDA5; ISG56; CXCL10; U373MG cells; Astrocytes
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Funding
- Hirosaki University
- Grants-in-Aid for Scientific Research [23592081] Funding Source: KAKEN
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Toll-like receptor (TLR) 4 is a pattern recognition receptor, and recognizes not only bacterial lipopolysaccharide (LPS) but also endogenous danger-associated molecular patterns released from dying or injured cells. It has been reported that TLR4 signaling in astrocytes plays an important role in various neurological diseases. However, details of TLR4 signaling in astrocytes are not fully elucidated. In the present study, we demonstrated that TLR4 signaling, induced by LPS, increases the expression of melanoma differentiation-associated gene 5 (MDA5) and interferon (IFN)-stimulated gene 56 (ISG56) in U373MG human astrocytoma cells. We also found that nuclear factor-kappa B, p38 mitogen-activated protein kinase and IFN-beta are involved in the expression of MDA5 and ISG56 induced by LPS. RNA interference experiments revealed that MDA5 and ISG56 positively regulate the LPS-induced expression of a chemokine CXCL10, but not CCL2. In addition, it was suggested that MDA5 and ISG56 constitute a positive feedback loop. These results suggest that MDA5 and ISG56 may contribute not only to physiological inflammatory reactions but also to the pathogenesis of various neurological diseases elicited by TLR4 in astrocytes, at least in part, by regulating the expression of CXCL10. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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