ROS-deficient monocytes have aberrant gene expression that correlates with inflammatory disorders of chronic granulomatous disease

Kelly L. Brown, Johan Bylund, Kelly L. MacDonald, George X. Song-Zhao, Melissa R. Elliott, Reza Falsafi, Robert Hancock, David P. Speert

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Chronic granulomatous disease is an immunodeficiency caused by an inability to produce reactive oxygen species. While the mechanism of hyper-sensitivity to infection is well understood in CGD, the basis for debilitating inflammatory disorders that arise in the absence of evident infection has not been fully explained. Herein it is demonstrated that resting and TLR-activated monocytes from individuals with CGD expressed significantly higher levels of inflammatory mediators than control cells; the expression in CGD cells resembled normal cells stimulated with lipopolysaccharide. The lack of acute illness, infection or circulating endotoxin in the blood of the CGD patients at the time of sampling was consistent with infection-free inflammation. The enhanced expression of inflammatory mediators correlated with elevated expression of NF-κB and was dependent on ERK1/2 signalling. The results are consistent with the hypothesis that ROS are anti-inflammatory mediators that control gene expression and potentially limit the development of sterile inflammatory disorders.

Original languageEnglish
Pages (from-to)90-102
Number of pages13
JournalClinical Immunology
Volume129
Issue number1
DOIs
Publication statusPublished - 1 Oct 2008
Externally publishedYes

Keywords

  • Cytokines
  • Gene regulation
  • Inflammation
  • Lipopolysaccharide
  • Reactive oxygen species

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this