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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalExperimental Lung Research
DOIs
Publication statusAccepted/In press - 2016 Apr 28

Fingerprint

Tobacco
Smoke
Pneumonia
Phosphotransferases
Macrophages
Bronchoalveolar Lavage Fluid
Chemokines
Neutrophils
Smoking
Fluids
Tissue
Lung
Bronchoalveolar Lavage
PS1145
Knockout Mice
Cell Count
Control Groups

Keywords

  • I-kappa B kinase inhibitor
  • lung injury
  • tobacco smoke

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

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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.",
keywords = "I-kappa B kinase inhibitor, lung injury, tobacco smoke",
author = "Choi, {Sue In} and Lee, {Sang Yeub} and Jung, {Won Jai} and Lee, {Seung Hyeun} and Lee, {Eun Joo} and Kyung-Hoon Min and Hur, {Gyu Young} and Lee, {Seung Heon} and Lee, {Sung Yong} and Kim, {Je Hyeong} and Chol Shin and Shim, {Jae Jeong} and In, {Kwang Ho} and Kang, {Kyung Ho} and Min-Goo Lee",
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T1 - The effect of an IκB-kinase-β(IKKβ) inhibitor on tobacco smoke-induced pulmonary inflammation

AU - Choi, Sue In

AU - Lee, Sang Yeub

AU - Jung, Won Jai

AU - Lee, Seung Hyeun

AU - Lee, Eun Joo

AU - Min, Kyung-Hoon

AU - Hur, Gyu Young

AU - Lee, Seung Heon

AU - Lee, Sung Yong

AU - Kim, Je Hyeong

AU - Shin, Chol

AU - Shim, Jae Jeong

AU - In, Kwang Ho

AU - Kang, Kyung Ho

AU - Lee, Min-Goo

PY - 2016/4/28

Y1 - 2016/4/28

N2 - 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.

AB - 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.

KW - I-kappa B kinase inhibitor

KW - lung injury

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