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

Choi, Sue In; Lee, Sang Yeub; Jung, Won Jai; Lee, Seung Hyeun; Lee, Eun Joo; Min, Kyung Hoon; Hur, Gyu Young; Lee, Seung Heon; Lee, Sung Yong; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Lee, Min-Goo

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.

NF-kappa B; TOBACCO smoke; LUNG diseases; INFLAMMATION; CHEMOKINES

Experimental Lung Research, 2016, Vol 42, Issue 4, p182

0190-2148

Academic Journal

10.1080/01902148.2016.1174749