Faculty Collaboration Database

Phosphatidylinositol 3-kinase regulates macrophage responses to double-stranded RNA and encephalomyocarditis virus. J Innate Immun 2010;2(1):77-86

Date

04/09/2010

Pubmed ID

20375625

Pubmed Central ID

PMC2943520

DOI

10.1159/000243785

Scopus ID

2-s2.0-77953430564 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Virus infection of macrophages stimulates the expression of proinflammatory and antiviral genes interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In this study, we show that phosphatidylinositol 3-kinase (PI3K) is required for the inflammatory response of macrophages to virus infection. When macrophages are infected with encephalomyocarditis virus (EMCV) there is a rapid and transient activation of PI3K and phosphorylation of its downstream target Akt. Inhibitors of PI3K attenuate EMCV- and double-stranded RNA-induced iNOS, COX-2 and IL-1 beta expression in RAW264.7 cells and mouse peritoneal macrophages. The attenuation of inflammatory gene expression in response to PI3K inhibition correlates with the induction of macrophage apoptosis. The morphology of macrophages shifts from activation in response to EMCV infection to apoptosis in the cells treated with PI3K inhibitors and EMCV. These morphological changes are accompanied by the activation of caspase-3. These findings suggest that PI3K plays a central role in the regulation of macrophage responses to EMCV infection. When PI3K is activated, it participates in the regulation of inflammatory gene expression; however, if PI3K is inhibited macrophages are unable to mount an inflammatory antiviral response and die by apoptosis.

Author List

Freudenburg W, Moran JM, Lents NH, Baldassare JJ, Buller RM, Corbett JA

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cardiovirus Infections
Caspase 3
Cell Line
Cyclooxygenase 2
Encephalomyocarditis virus
Interleukin-1beta
Macrophage Activation
Macrophages, Peritoneal
Mice
Mice, Inbred C57BL
Nitric Oxide
Nitric Oxide Synthase Type II
Phosphatidylinositol 3-Kinases
Phosphorylation
Proto-Oncogene Proteins c-akt
RNA, Double-Stranded