Asthma is characterized by airway inflammation with intense eosinophil infiltration and MUCUS hyperproduction, 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 GS 143, 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. (C) 2008 Elsevier Inc. All rights reserved.