Cross-talk between the TRAIL and TGFβ pathways in regulation of collagen production by lung fibroblasts

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was found on CD8 T cells that underwent oligoclonal expansion in the lungs of patients with systemic sclerosis and were able to stimulate collagen production in lung fibroblasts in vitro. Soluble multimerized TRAIL and normal human lung fibroblasts were used as a model of selective TRAIL influence on fibroblasts. TRAIL at doses greater than or equal to100 ng/ml induced cell apoptosis. However, at lower doses it was found to stimulate collagen expression, with peak response at 1 ng/ml TRAIL. DNA microarray analysis revealed the TRAIL-induced increase in the expression of genes involved in tissue remodeling, including those related to the transforming growth factor-P (TGFbeta) pathway. Anti-TGFbeta antibody was shown to abrogate the TRAIL-induced collagen synthesis. These data suggest that TRAIL can enhance extracellular matrix production in fibroblasts by triggering TGFbeta expression, which acts in an autocrine manner.