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

Abstract

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.

• Authors: Sue In Choi, Sang Yeub Lee, Won Jai Jung, Seung Hyeun Lee, Eun Joo Lee, Kyung Hoon Min, Gyu Young Hur, Seung Heon Lee, Sung Yong Lee, Je Hyeong Kim, Chol Shin, Jae Jeong Shim, Kwang Ho In, Kyung Ho Kang, Min-Goo Lee
• Journal: Experimental lung research (Exp Lung Res) Vol. 42 Issue 4 Pg. 182-9 (05 2016) ISSN: 1521-0499 [Electronic] England
• PMID: 27144414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Heterocyclic Compounds, 3-Ring
• NF-kappa B
• PS1145
• Protein Kinase Inhibitors
• Pyridines
• Tobacco Smoke Pollution
• I-kappa B Kinase

Topics

• Animals
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Cell Count
• Chemokines (drug effects, metabolism)
• Heterocyclic Compounds, 3-Ring (administration & dosage, pharmacology)
• I-kappa B Kinase (antagonists & inhibitors)
• Macrophages, Alveolar (drug effects, pathology)
• Mice
• NF-kappa B (drug effects, metabolism)
• Neutrophils (drug effects, pathology)
• Pneumonia (etiology, pathology)
• Protein Kinase Inhibitors (administration & dosage, pharmacology)
• Pyridines (administration & dosage, pharmacology)
• Tobacco Smoke Pollution (adverse effects)