Cysteinyl leukotrienes regulate TGF-β1 and collagen production by bronchial fibroblasts obtained from asthmatic subjects

被引:34
作者
Eap, R. [1 ]
Jacques, E. [1 ]
Semlali, A. [1 ]
Plante, S. [1 ]
Chakir, J. [1 ]
机构
[1] Ctr Rech Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ G1V 4G5, Canada
来源
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS | 2012年 / 86卷 / 03期
关键词
Airway remodeling; Asthma; Fibroblasts; Leukotrienes; Montelukast; MUSCLE-CELL PROLIFERATION; RECEPTOR ANTAGONIST; IN-VITRO; EXPRESSION; MYOFIBROBLASTS; MONTELUKAST; INFLAMMATION; FIBROSIS; AIRWAYS; LUNG;
D O I
10.1016/j.plefa.2011.11.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Background: Cysteinyl leukotrienes (CysLTs) play an important role in airway inflammation in asthma but their role in airway remodeling is not completely known. Methods: CysLTs receptors and procollagen I(alpha(1)) mRNA were determined by qPCR. Procollagen protein production was measured by RIA and TGF-beta(1) expression was determined by ELISA. TGF-beta receptor expression was assessed by western blots. Results: CysLI1R, TGF-beta-R1 and active TGF-beta(1) are highly expressed in cells from asthmatics compared to normal controls. LTD4 increased significantly procollagen I(alpha(1)) mRNA and piotein expression in fibroblasts from asthmatics. This increase was blocked by CysLTs receptor antagonist. LTD4 increased significantly mRNA expression of TGF-beta(1) and active form production in fibroblasts from asthmatics. Inhibition of TGF-beta(1) signaling blocked LTD4-induced procollagen I(alpha(1)) expression. Conclusions: Fibroblasts from asthmatic subjects express high level of CysLT1R. LTD4 regulates procollagen I(alpha(1)) transcription in fibroblasts derived from asthmatic patients by modulating TGF-beta(1) expression. This suggests that CysLTs may play a role in regulating collagen deposition in asthma. Crown Copyright (C) 2012 Published by Elsevier Ltd All rights reserved.
引用
收藏
页码:127 / 133
页数:7
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