The effect of an IκB-kinase-β(IKKβ) inhibitor on tobacco smoke-induced pulmonary inflammation

Purpose of the Study: Inactivation of NF-κB with IKKβ knockout mice reduces tobacco smoke-induced pulmonary inflammation. In this study, we investigated whether the IKKβ inhibitor PS-1145 could attenuate the pulmonary inflammation induced by tobacco smoke. Materials and Methods: We divided 30 mice into three groups: a control group, a smoking group, and a PS-1145 group. Mice from the smoking and PS-1145 groups were exposed for 2 weeks to tobacco smoke. PS-1145 was injected intraperitoneally before every tobacco smoke exposure. After 2 weeks, bronchoalveolar lavage (BAL) was performed for cell counting and measuring of inflammatory chemokines. We analyzed the correlation between NF-κB and NF-κB-regulated chemokines in BAL fluid and measured the neutrophils and macrophages by immunostaining in lung tissues. Results: The PS-1145 group showed a significant reduction in the number of total cells, neutrophils, and macrophages, as well as the KC and MCP-1 level, in the BAL fluid compared to the smoking group. There was no significant difference in the level of MIP-1α. The level of NF-κB in BAL fluid was significantly positively correlated with KC and MCP-1 levels, but not with MIP-1α level. The PS-1145 group also showed a significant fewer neutrophils and macrophages in the lung tissue. Conclusions: We conclude that the IKKβ inhibitor PS-1145 suppressed the NF-κB signaling pathway and reduced the recruitment of inflammatory cells and chemokines in pulmonary inflammation induced by tobacco smoke. IKKβ inhibition offers a potential therapeutic target for tobacco smoke-induced pulmonary inflammation.