Redox regulation in metabolic programming and inflammation

Helen R. Griffiths, Dan Gao, Chathyan Pararasa

Research output: Contribution to journalReview article

Abstract

Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs. Later on, the most prevalent recruited innate immune cells are monocytes. Their role is to complete a damage limitation exercise initiated by neutrophils and then, as re-programmed M2 macrophages, to resolve the inflammatory event. Almost twenty five years ago, it was noted that macrophages lose their glycolytic capacity and become anti-inflammatory after treatment with corticosteroids. In support of this we now understand that, in contrast to early responders, M2 macrophages are predominantly dependent on oxidative phosphorylation for energy. During early inflammation, polarisation towards M1 macrophages is dependent on NOX2 activation which, via protein tyrosine phosphatase oxidation and AKT activation, increases trafficking of glucose transporters to the membrane and consequently increases glucose uptake for glycolysis. In parallel, mitochondrial efficiency is likely to be compromised via nitrosylation of the electron transport chain. Resolution of inflammation is triggered by encounter with apoptotic membranes exposing oxidised phosphatidylserine that interact with the scavenger receptor, CD36. Downstream of CD36, activation of AMPK and PPARγ elicits mitochondrial biogenesis, arginase expression and a switch towards oxidative phosphorylation in the M2 macrophage. Proinflammatory cytokine production by M2 cells decreases, but anti-inflammatory and wound healing growth factor production is maintained to support restoration of normal function.

LanguageEnglish
Pages50-57
Number of pages8
JournalRedox biology
Volume12
Early online date12 Feb 2017
DOIs
Publication statusPublished - Aug 2017

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Macrophages
Oxidation-Reduction
Inflammation
Neutrophils
Chemical activation
Oxidative Phosphorylation
Glycolysis
Bacterial Physiological Phenomena
Anti-Inflammatory Agents
Membranes
Hypochlorous Acid
Scavenger Receptors
Arginase
AMP-Activated Protein Kinases
Protein Tyrosine Phosphatases
Facilitative Glucose Transport Proteins
Phosphatidylserines
Organelle Biogenesis
Energy resources
Electron Transport

Bibliographical note

© 2017 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).

Funding: BBSRC (China Partnering Award BB/M028100/1 and Targeted Priority Studentship in Ageing BB/G017832/1); and the Glenn Foundation for Aging Research.

Cite this

Griffiths, Helen R. ; Gao, Dan ; Pararasa, Chathyan. / Redox regulation in metabolic programming and inflammation. In: Redox biology. 2017 ; Vol. 12. pp. 50-57.
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Redox regulation in metabolic programming and inflammation. / Griffiths, Helen R.; Gao, Dan; Pararasa, Chathyan.

In: Redox biology, Vol. 12, 08.2017, p. 50-57.

Research output: Contribution to journalReview article

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AU - Griffiths, Helen R.

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AU - Pararasa, Chathyan

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