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The Raf-1 inhibitor...
The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice
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- Lei, Ying (author)
- Lund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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Cao, Yong-Xiao (author)
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- Xu, Cang-Bao (author)
- Lund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Zhang, Yaping (author)
- Karolinska Institutet,Lund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk och experimentell allergiforskning,Laryngoesofagologi, allergi och livskvalitet,Forskargrupper vid Lunds universitet,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical and Experimental Allergy Research,Laryngoesophagology, Allergy and Life Quality,Lund University Research Groups
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(creator_code:org_t)
- 2008-11-03
- 2008
- English.
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In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 9
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Abstract
Subject headings
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- Background: Sidestream smoke is closely associated with airway inflammation and hyperreactivity. The present study was designed to investigate if the Raf-1 inhibitor GW5074 and the anti-inflammatory drug dexamethasone suppress airway hyperreactivity in a mouse model of sidestream smoke exposure. Methods: Mice were repeatedly exposed to smoke from four cigarettes each day for four weeks. After the first week of the smoke exposure, the mice received either dexamethasone intraperitoneally every other day or GW5074 intraperitoneally every day for three weeks. The tone of the tracheal ring segments was recorded with a myograph system and concentration-response curves were obtained by cumulative administration of agonists. Histopathology was examined by light microscopy. Results: Four weeks of exposure to cigarette smoke significantly increased the mouse airway contractile response to carbachol, endothelin-1 and potassium. Intraperitoneal administration of GW5074 or dexamethasone significantly suppressed the enhanced airway contractile responses, while airway epithelium-dependent relaxation was not affected. In addition, the smoke-induced infiltration of inflammatory cells and mucous gland hypertrophy were attenuated by the administration of GW5074 or dexamethasone. Conclusion: Sidestream smoke induces airway contractile hyperresponsiveness. Inhibition of Raf-1 activity and airway inflammation suppresses smoking-associated airway hyperresponsiveness.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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