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CCR5-Dependent Activation of mTORCl Regulates Translation of Inducible NO Synthase and COX-2 during Encephalomyocarditis Virus Infection.
- Source :
-
Journal of Immunology . 11/1/2015, Vol. 195 Issue 9, p4406-4414. 9p. - Publication Year :
- 2015
-
Abstract
- Encephalomyocarditis virus (EMCV) infection of macrophages results in the expression of a number of inflammatory and antiviral genes, including inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. EMCV-induced macrophage activation has been shown to require the presence of CCR5 and the activation of PI3K-dependent signaling cascades. The purpose of this study was to determine the role of PI3K in regulating the macrophage responses to EMCV. We show that PI3K regulates EMCV-stimulated iNOS and COX-2 expression by two independent mechanisms. In response to EMCV infection, Akt is activated and regulates the translation of iNOS and COX-2 through the mammalian target of rapamycin complex (mTORC)1. The activation of mTORC1 during EMCV infection is CCR5-dependent and appears to function in a manner that promotes the translation of iNOS and COX-2. CCR5-dependent mTORC1 activation functions as an antiviral response, as mTORC1 inhibition increases the expression of EMCV polymerase. PI3K also regulates the transcriptional induction of iNOS and COX-2 in response to EMCV infection by a mechanism that is independent of Akt and mTORC1 regulation. These findings indicate that macrophage expression of the inflammatory genes iNOS and COX-2 occurs via PI3K- and Akt-dependent translational control of mTORC1 and PI3K-dependent, Akt-independent transcriptional control. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 195
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 112149392
- Full Text :
- https://doi.org/10.4049/jimmunol.1500704