Aldose reductase inhibition suppresses the expression of Th2 cytokines and airway inflammation in ovalbumin-induced asthma in mice

Umesh C.S. Yadav, Amarjit S. Naura, Leopoldo Aguilera-Aguirre, Kota V. Ramana, Istvan Boldogh, Sanjiv Sur, Hamid A. Boulares, Satish K. Srivastava

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Airway inflammation induced by reactive oxygen species-mediated activation of redox-sensitive transcription factors is the hallmark of asthma, a prevalent chronic respiratory disease. In various cellular and animal models, we have recently demonstrated that, in response to multiple stimuli, aldose reductase (AR) regulates the inflammatory signals mediated by NF-κB. Because NF-κB-mediated inflammation is a major characteristic of asthma pathogenesis, we have investigated the effect of AR inhibition on NF-κB and various inflammatory markers in cellular and animal models of asthma using primary human small airway epithelial cells and OVA-sensitized/challenged C57BL/6 mice, respectively. We observed that pharmacological inhibition or genetic ablation of AR by small interfering RNA prevented TNF-α- as well as LPS-induced apoptosis; reactive oxygen species generation; synthesis of inflammatory markers IL-6, IL-8, and PGE2; and activation of NF-κB and AP-1 in small airway epithelial cells. In OVA-challenged mice, we observed that administration of an AR inhibitor markedly reduced airway hyperresponsiveness, IgE levels, eisonophils infiltration, and release of Th2 type cytokines in the airway. Our results indicate that AR inhibitors may offer a novel therapeutic approach to treat inflammatory airway diseases such as asthma.

Original languageEnglish (US)
Pages (from-to)4723-4732
Number of pages10
JournalJournal of Immunology
Volume183
Issue number7
DOIs
StatePublished - Oct 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yadav, U. C. S., Naura, A. S., Aguilera-Aguirre, L., Ramana, K. V., Boldogh, I., Sur, S., Boulares, H. A., & Srivastava, S. K. (2009). Aldose reductase inhibition suppresses the expression of Th2 cytokines and airway inflammation in ovalbumin-induced asthma in mice. Journal of Immunology, 183(7), 4723-4732. https://doi.org/10.4049/jimmunol.0901177