کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2568008 1561153 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury
چکیده انگلیسی


• Inhalation of Cl2 leads to acute lung inflammation and airway hyperreactivity.
• Cl2 activates an inflammasome pathway of TGF-β induction.
• Cl2 leads to a fibrotic respiratory disease.
• Treatment with corticosteroids alone is insufficient to counteract acute lung injury.

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl2) with the aim to understand the pathogenesis of the long-term sequelae of Cl2-induced lung-injury.In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl2. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl2-exposure.A 15-min inhalation of 200 ppm Cl2 was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl2-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR.Inhalation of Cl2 in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl2-induced respiratory dysfunction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 309, 15 October 2016, Pages 44–54
نویسندگان
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