GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice
- Department of Allergy and Clinical Immunology, Chiba University Hospital (Japan)
- Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba (Japan)
- GeneCare Research Institute Co., Ltd., Kanagawa (Japan)
Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-{kappa}B (NF-{kappa}B) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil and lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.
- OSTI ID:
- 21143882
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 374; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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