Cysteinyl leukotrienes regulate TGF-β(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects.
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(α(1)) mRNA were determined by qPCR. Procollagen protein production was measured by RIA and TGF-β(1) expression was determined by ELISA. TGF-β receptor expression was assessed by western blots.


RESULTS
CysLT1R, TGF-β-R1 and active TGF-β(1) are highly expressed in cells from asthmatics compared to normal controls. LTD(4) increased significantly procollagen I(α(1)) mRNA and protein expression in fibroblasts from asthmatics. This increase was blocked by CysLTs receptor antagonist. LTD(4) increased significantly mRNA expression of TGF-β(1) and active form production in fibroblasts from asthmatics. Inhibition of TGF-β(1) signaling blocked LTD(4)-induced procollagen I(α(1)) expression.


CONCLUSIONS
Fibroblasts from asthmatic subjects express high level of CysLT1R. LTD(4) regulates procollagen I(α(1)) transcription in fibroblasts derived from asthmatic patients by modulating TGF-β(1) expression. This suggests that CysLTs may play a role in regulating collagen deposition in asthma.
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
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R
Eap
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E
Jacques
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A
Semlali
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Plante
J
J
Chakir
D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003545:Cysteine / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D015289:Leukotrienes / Q000494:pharmacology*; D008297:Male; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D007155:Immunologic Factors; D015289:Leukotrienes; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C112381:cysteinyl-leukotriene; D003094:Collagen; D003545:Cysteine