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

SummaryBackgroundCysteinyl leukotrienes (CysLTs) play an important role in airway inflammation in asthma but their role in airway remodeling is not completely known.MethodsCysLTs receptors and procollagen I(α1) mRNA were determined by qPCR. Procollagen protein production was measured by RIA and TGF-β1 expression was determined by ELISA. TGF-β receptor expression was assessed by western blots.ResultsCysLT1R, TGF-β-R1 and active TGF-β1 are highly expressed in cells from asthmatics compared to normal controls. LTD4 increased significantly procollagen I(α1) mRNA and protein expression in fibroblasts from asthmatics. This increase was blocked by CysLTs receptor antagonist. LTD4 increased significantly mRNA expression of TGF-β1 and active form production in fibroblasts from asthmatics. Inhibition of TGF-β1 signaling blocked LTD4-induced procollagen I(α1) expression.ConclusionsFibroblasts from asthmatic subjects express high level of CysLT1R. LTD4 regulates procollagen I(α1) transcription in fibroblasts derived from asthmatic patients by modulating TGF-β1 expression. This suggests that CysLTs may play a role in regulating collagen deposition in asthma.