Elsevier

Kidney International

Volume 70, Issue 4, 2 August 2006, Pages 788-793
Kidney International

Original Article
Interferon-γ enhances superoxide production in human mesangial cells via the JAK–STAT pathway

https://doi.org/10.1038/sj.ki.5001639Get rights and content
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Immune reactive cytokines, such as interferon (IFN)-γ, have multiple effects in glomerulonephritis. Superoxide anions (O2), which are associated with the progression of glomerulonephritis, are mainly generated by nicotinamide adenine dinucleotide phosphate (reduced form) NAD(P)H oxidases. We determined the effects of IFN-γ on O2 production, phosphorylation of signal transducer and activator of transcription (STAT)-1α, and the mRNA and protein expressions of p22phox and Nox1, components of NAD(P)H oxidases, in human mesangial cells (HMCs). Significant increases in O2 production with IFN-γ were completely abolished by the flavin-containing enzyme inhibitor, diphenyleneiodonium (10 μmol/l), and the Janus-activated kinase (JAK)2 inhibitor, AG490 (100 μmol/l). Phosphorylated STAT-1α was detected after 5 min of IFN-γ stimulation using Western blot analysis, and binding to the gamma-activating site was observed from 30 min to 4 h, thereafter by electrophoretic mobility shift assay (EMSA). Super-shift analysis in EMSA revealed that the main transcription factor was STAT-1α. IFN-γ significantly increased the expression of p22phox mRNA and protein, although expression was inhibited by AG490. These data suggest that IFN-γ stimulates O2 production in HMCs via the JAK–STAT pathway and NAD(P)H oxidase.

KEYWORDS

cytokines
reactive oxygen species
mesangial cells
cell signaling
glomerulopathy

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