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Obstructive Lung Diseases |

Effects of Zileuton on Airway Remodeling and TGF-β mRNA Expression After Repeated Allergen Challenge: An Animal Model

Ching-Chi Lin*, MD; Shwu-Fang Liaw, MS; Mei-Wei Lin, BS; Feng-Ting Chang, BS
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Mackay Memorial Hospital, Taipei, Taiwan


Chest. 2012;142(4_MeetingAbstracts):687A. doi:10.1378/chest.1389347
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Abstract

SESSION TYPE: Asthma Treatment

PRESENTED ON: Monday, October 22, 2012 at 11:15 AM - 12:30 PM

PURPOSE: Chronic asthma is characterized by airway inflammation and remodeling. The purpose of this study was to evaluate the effects of Zileuton on airway remodeling and TGF-β mRNA expression in brown-Norway rats (BNR) after repeated ovalbumin challenge.

METHODS: Two experimental groups of BNR sensitized and repeatedly challenged with aerosolized ovalbumin were given oral Zileuton (OA-Zileuton group) (n = 8) and oral saline only (OA-saline group) (n = 8), respectively. A third control group (n = 8) were sensitized and challenged by saline. The rats were anesthetized and paralyzed, and bronchoalveolar lavage were performed. Bronchoalveolar lavage fluid and TGF-β, VEGF and their mRNA expression were examined. Lung tissues were stained with haematoxylin and eosin, Masson’s trichrome, smooth muscle actin, and von Willebrand factor for microscopic examination for evaluating lung tissues remodeling.

RESULTS: Our results showed that Zileuton had beneficial effects on TGF-β, VEGF and their mRNA expression in the OA-Zileuton group compared to the OA-saline group. OA-saline group had more severe lung inflammation, than the other 2 groups. The airway inflammation, area of collagen deposition surrounding the airways, the mean thickness of the smooth muscle layer surrounding the airways, the mean number of the blood vessels surrounding the airways were lowest in the control group compared to the other 2 groups and significantly lower in the OA-Zileuton group compared to the OA-saline group. The mean fold change of thickening of basement membrane relative to the control group was 1.8-fold in the OA-Zileuton group and 3.3-fold in the OA-saline group. The mean fold-change of thickening of smooth muscle relative to the control group was 1.5-fold in the OA-Zileuton group and 2.0-fold in the OA-saline group.

CONCLUSIONS: Zileuton is effective in preventing airway inflammation, TGF-β mRNA expression, and airway remodeling after sensitization and repeated allergen challenge in a rat model.

CLINICAL IMPLICATIONS: Zileuton is effective in preventing airway remodeling after repeated allergen challenge in a rat model.

DISCLOSURE: The following authors have nothing to disclose: Ching-chi Lin, Shwu-Fang Liaw, Mei-Wei Lin, Feng-Ting Chang

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Mackay Memorial Hospital, Taipei, Taiwan

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