Cysteinyl leukotrienes (CysLTs) play an important role in the pathogenesis of airway remodeling. We investigated the interaction between epithelium and CysLTC(4), and the contribution of this interaction to airway fibrosis. Human airway epithelial cells were grown on air-liquid interface culture inserts. CysLTC(4) was employed to stimulate the cells. Conditioned medium following CysLTC(4) stimulation was coincubated with human lung fibroblasts. Our results have demonstrated that CysLTC(4) stimulates airway epithelial cells, through a p38 mitogen-activated protein kinase (MAPK) activation mechanism, to produce transforming growth factor beta(1) (TGF-beta(1)), which results in fibroblast proliferation. The selective p38 MAPK inhibitor S203580 successfully inhibits p38 MARK phosphorylation and subsequent TGF-beta(1) production. CysLT(1) receptor antagonist montelukast and corticosteroid inhibit TGF-beta(1) production at the mRNA and protein levels. When treated with LTC4, the conditioned medium from epithelial cells enhances fibroblast proliferation, this mitogenic effect being attributed to TGF-beta(1) and LTC4 remaining in the culture medium. In addition, LTC4 itself acts as a potential growth factor for lung fibroblasts. These data indicate that interactions between LTC4 and airway epithelial cells may contribute to the pathogenesis of airway remodeling. Early intervention to stop these processes may be useful in preventing airway fibrosis in chronic allergic inflammation.
Date:
2006-01
Relation:
American Journal of Respiratory Cell and Molecular Biology. 2006 Jan;34(1):101-107.
