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

• 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-kappaB 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.

Nyckelord

Adolescent

Adult

Cytokines/biosynthesis/*genetics/immunology

Extracellular Signal-Regulated MAP Kinases/metabolism

Gene Expression Profiling

Granulomatous Disease

Chronic/genetics/*immunology/metabolism

Humans

Inflammation Mediators/immunology/*metabolism

Male

Monocytes/*immunology/metabolism

Oligonucleotide Array Sequence Analysis

Protein-Serine-Threonine Kinases/metabolism

Reactive Oxygen Species/*metabolism

Signal Transduction

Toll-Like Receptors/*immunology

p38 Mitogen-Activated Protein Kinases/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)