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AB0010 Increased collagen production by human lung fibroblasts in the response to tumour necrosis factor-related apoptosis-inducing ligand
  1. VV Yurovsky
  1. Department of Medicine, University of Maryland, Baltimore, USA

Abstract

Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), also called Apo-2 ligand, is a member of the TNF family that has been reported to induce apoptosis in a variety of transformed cell lines, as well as in normal human hepatocytes in vitro. Among the family members, TRAIL displays highest homology to CD95 ligand, receptor of which may not only mediate apoptosis of T cells, but also mediate the proliferation of normal human fibroblasts. Considering structural and functional similarities between TRAIL and CD95 ligand, we examined the effects of soluble TRAIL on normal human lung fibroblasts. Collagen a2(I) mRNA expression in fibroblasts was measured by RT-PCR, with ribosomal protein S9 as an internal standard. Normalised collagen mRNA expression was increased in fibroblasts stimulated with TRAIL for 1 or 7 days, with peak response (> 5-fold increase) at 10 ng/ml TRAIL. The increased expression of collagen a2(I) gene was confirmed by cDNA microarray that also revealed 72 other genes with expression level increased and 108 genes with expression level decreased ª 2.2-fold in comparison with quiescent fibroblasts. There was little, if any, effect of TRAIL on fibroblast proliferation. The expression of TRAIL was also found in CD8+ T cell clones that had undergone oligoclonal expansion in the lungs of patients with systemic sclerosis (scleroderma) and were able to stimulate collagen production in lung fibroblasts in vitro. These data suggest that TRAIL can enhance collagen production by fibroblasts that are resistant to TRAIL-induced apoptosis.

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