GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway

Menon, Deepthi, Coll, Rebecca, O'Neill, Luke A. J and Board, Philip G (2015) GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway. Journal of Cell Science, 128 10: 1982-1990. doi:10.1242/jcs.167858

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Author Menon, Deepthi
Coll, Rebecca
O'Neill, Luke A. J
Board, Philip G
Title GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 1477-9137
0021-9533
Publication date 2015-05-15
Year available 2015
Sub-type Article (original research)
DOI 10.1242/jcs.167858
Open Access Status File (Publisher version)
Volume 128
Issue 10
Start page 1982
End page 1990
Total pages 9
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Collection year 2016
Language eng
Abstract Macrophages mediate innate immune responses that recognise foreign pathogens, and bacterial lipopolysaccharide (LPS) recruits a signalling pathway through Toll-like receptor 4 (TLR4) to induce pro-inflammatory cytokines and reactive oxygen species (ROS). LPS activation also skews the metabolism of macrophages towards a glycolytic phenotype. Here, we demonstrate that the LPS-triggered glycolytic switch is significantly attenuated in macrophages deficient for glutathione transferase omega-1 (GSTO1, note that GSTO1-1 refers to the dimeric molecule with identical type 1 subunits). In response to LPS, GSTO1-1-deficient macrophages do not produce excess lactate, or dephosphorylate AMPK, a key metabolic stress regulator. In addition, GSTO1-1-deficient cells do not induce HIF1α, which plays a key role in maintaining the pro-inflammatory state of activated macrophages. The accumulation of the TCA cycle intermediates succinate and fumarate that occurs in LPS-treated macrophages was also blocked in GSTO1-1-deficient cells. These data indicate that GSTO1-1 is required for LPS-mediated signalling in macrophages and that it acts early in the LPS–TLR4 pro-inflammatory pathway.
Keyword Metabolism
GSTO1-1
TLR4
Redox
LPS
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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