DIFFERENTIAL CYTOKINE REGULATION OF TYPE-I AND TYPE-VII COLLAGEN GENE-EXPRESSION IN CULTURED HUMAN DERMAL FIBROBLASTS

Type VII collagen is the major component of anchoring fibrils in the c utaneous basement membrane zone. In this study, we have examined the e ffects of various cytokines on the expression of types I and VII colla gen genes in dermal fibroblasts in culture. The pro-inflammatory cytok ines, interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), tu mor necrosis factor-alpha (TNF-alpha), and leukoregulin (LR) strongly elevated (approximately 5-9-fold) type VII collagen mRNA levels, as me asured by Northern blot hybridizations. These effects were also observ ed at the protein level by indirect immunofluorescence using a monoclo nal antibody specific for type VII collagen. By contrast, IL-1beta had only a slight stimulatory effect (approximately 2-fold) on type I col lagen gene expression, while TNF-alpha and LR markedly reduced type I collagen mRNA steady-state levels. Interestingly, IL-1, TNF-alpha and LR had additive effects with transforming growth factor-beta (TGF-beta ) on type VII collagen gene expression, whereas they counteracted the up-regulatory effect of TGF-beta on type I collagen gene expression. T hus, our data indicate that the modulation of type I and type VII coll agen gene expression by cytokines involves different regulatory pathwa ys.