title: The effect of an IκB-kinase-β(IKKβ) inhibitor on tobacco smoke-induced pulmonary inflammation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Sue In
authors.initials: SI
authors.lastname: Choi
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Won Jai
authors.initials: WJ
authors.lastname: Jung
authors.affiliation: b Division of Pulmonary and Critical Care Medicine , Department of Internal Medicine, Kyung Hee University School of Medicine , Seoul , Korea.
authors.forename: Seung Hyeun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Hur
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
authors.affiliation: a Division of Respiratory and Critical Care Medicine , Department of Internal Medicine, College of Medicine, Korea University , Seoul , Korea.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.affiliation: c Department of Physiology , College of Medicine, Korea University , Seoul , Korea.
authors.forename: Min-Goo
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D018925:Chemokines; D006575:Heterocyclic Compounds, 3-Ring; D016328:NF-kappa B; C456319:PS1145; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014028:Tobacco Smoke Pollution; D051550:I-kappa B Kinase
keywords: I-kappa B kinase inhibitor; lung injury; tobacco smoke