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Leukotriene D 4 ‐induced, epithelial cell‐derived transforming growth factor β1 in human bronchial smooth muscle cell proliferation
Author(s) -
Bossé Y.,
Thompson C.,
McMahon S.,
Dubois C. M.,
Stankova J.,
RolaPleszczynski M.
Publication year - 2008
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2007.02873.x
Subject(s) - transforming growth factor , cell growth , cell culture , immunology , leukotriene d4 , microbiology and biotechnology , medicine , biology , cancer research , leukotriene , asthma , genetics
Summary Background Cysteinyl‐leukotrienes (cys‐LTs) orchestrate many pathognomonic features of asthma in animal models of allergic airway inflammation, including bronchial smooth muscle cell (BSMC) hyperplasia. However, because cys‐LTs alone do not induce mitogenesis in monocultures of human BSMC, the effect observed in vivo seemingly involves indirect mechanisms, which are still undefined. Objective This study aims to investigate the regulatory role of leukotriene (LT)D 4 on TGF‐β1 expression in airway epithelial cells and the consequence of this interplay on BSMC proliferation. Methods HEK293 cells stably transfected with cys‐LT receptor 1 (CysLT1) (293LT1) were stimulated with LTD 4 and TGF‐β1 mRNA and protein expression was measured using Northern blot and ELISA, respectively. Conditioned medium (CM) harvested from LTD 4 ‐treated cells was then assayed for its proliferative effect on primary human BSMC. TGF‐β1 mRNA expression was also determined in tumoural type II pneumocytes A549 and in normal human bronchial epithelial cells (NHBE) following LTD 4 stimulation. Results The results demonstrated that LTD 4 ‐induced TGF‐β1 mRNA production in a time‐ and concentration‐dependent manner in 293LT1. TGF‐β1 secretion was also up‐regulated and CM from LTD 4 ‐treated 293LT1 was shown to increase BSMC proliferation in a TGF‐β1‐dependent manner. The increased expression of TGF‐β1 mRNA by LTD 4 also occured in A549 and NHBE cells via a CysLT1‐dependent mechanism. Conclusion In conclusion, elevated expression of cys‐LTs in asthmatic airways might contribute to BSMC hyperplasia and concomitant clinical features of asthma such as airway hyperresponsiveness via a paracrine loop involving TGF‐β1 production by airway epithelial cells.