Glutathione transferase Omega 1 is required for the lipopolysaccharide- stimulated induction of NADPH oxidase 1 and the production of reactive oxygen species in macrophages

Deepthi Menon, Rebecca Coll, Luke A.J. O'Neill, Philip G. Board*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Bacterial lipopolysaccharide (LPS) stimulation of macrophages and inflammation via the Toll-like receptor 4 (TLR4) signaling pathway through NF-κΒ generates reactive oxygen species (ROS) and proinflammatory cytokines such as IL-1β, IL-6, and TNFα. Because glutathione transferase Omega 1-1 (GSTO1-1) can catalyze redox reactions such as the deglutathionylation of proteins and has also been implicated in the release of IL-1β we investigated its role in the development of LPS-mediated inflammation. Our data show that shRNA knockdown of GSTO1-1 in macrophage-like J774.1A cells blocks the expression of NADPH oxidase 1 and the generation of ROS after LPS stimulation. Similar results were obtained with a GSTO1-1 inhibitor. To maintain high ROS levels during an inflammatory response, LPS stimulation causes the suppression of enzymes such as catalase and glutathione peroxidase that protect against oxidative stress. The knockdown of GSTO1-1 also attenuates this response. Our data indicate that GSTO1-1 needs to be catalytically active and mediates its effects on the LPS/TLR4 inflammatory pathway upstream of NF-κΒ. These data suggest that GSTO1-1 is a novel target for anti-inflammatory intervention.

Original languageEnglish
Pages (from-to)318-327
Number of pages10
JournalFree Radical Biology and Medicine
Volume73
DOIs
Publication statusPublished - 01 Jan 2014
Externally publishedYes

Keywords

  • Free radicals
  • Glutathione transferase Omega 1
  • LPS
  • NADPH oxidase 1
  • TLR4

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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