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FEBS Lett. 2013 Mar 18;587(6):756-62. doi: 10.1016/j.febslet.2013.01.067. Epub 2013 Feb 8.

Inflammatory response of microglial BV-2 cells includes a glycolytic shift and is modulated by mitochondrial glucose-regulated protein 75/mortalin.

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  • 1Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, Grant Building S272, Stanford, CA 94305, United States. ludmilav@stanford.edu

Abstract

Recent studies suggest a link between mitochondria and proinflammatory cytokine generation. We previously demonstrated that overexpression of mitochondrial chaperone glucose-regulated protein75 (Grp75/mortalin) protects mitochondria. In this study we investigated the modulation of the lipopolisaccharide (LPS)-induced inflammatory response of microglial BV-2 cells by Grp75. We demonstrate that LPS-induced activation promotes significant metabolic changes suppressing mitochondrial function and increasing glycolysis. Overexpression of Grp75 attenuates the LPS-induced oxidative and metabolic responses, and suppresses proinflammatory activation, which depends on both NF-κB activation and lactate. Thus overexpression of Grp75 provides a novel strategy to modulate proinflammatory cytokine production of relevance to inflammation-associated pathologies.

Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PMID:
23395614
[PubMed - indexed for MEDLINE]
PMCID:
PMC3603371
Free PMC Article
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