Anti-inflammatory effects of inhibitors of the NF-kB pathway in the mouse asthma model

Abstract

The NF-kB family plays a key role in the initiation and development of asthma. Appropriate inhibition of NF-kB activity may be an effective anti-inflammatory strategy for asthma. My projects were to examine the effects of a GSK-3beta inhibitor, TDZD-8, and a herbal medicinal, andrographolide in an asthma model and elucidate their mechanisms in NF-kB pathway.Both TDZD-8 and andrographolide significantly inhibited ovalbumin-induced increases infiltration of inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid, Igs in serum, and mucus hypersecretion in lungs. These two drugs also suppressed airway hyperresponsiveness to methacholine in mice. Western blotting and TransAM assay of the whole lung and epithelial cells showed that TDZD-8 and andrographolide may exert its anti-inflammatory effects by inhibiting the phosphorylation of IKK2, or the DNA-binding activity of p65, or phosphorylation of p65.These findings implicate that appropriate inhibition of the NF-kB pathway may have therapeutic potential for asthma.