Platelet-derived growth factor and inflammatory cytokines have differential effects on the expression of integrins alpha 1 beta 1 and alpha 5 beta 1 by human dermal fibroblasts in vitro.

Dermal fibroblasts are essential for the repair of cutaneous wounds. Fibroblasts presumably use cell surface receptors of the integrin family during migration into a wound from the adjacent uninjured tissue and for the subsequent matrix repairs. We have investigated the possible roles of platelet-derived growth factor and inflammatory cytokines in the regulation of integrin expression on wound fibroblasts using a porcine cutaneous wound model and cultured human cells. Tissue specimens collected from 4-day pig wounds were stained with antibodies specific for the alpha 1 and alpha 5 integrin subunits. Staining for alpha 1 was markedly decreased on fibroblasts adjacent to the wound and in the granulation tissue, while staining for alpha 5 was clearly enhanced in both locations. Normal adult human dermal fibroblasts in culture express the integrins alpha 1 beta 1, a collagen receptor, and alpha 5 beta 1 a fibronectin receptor. Quantitative flow cytometry was used to measure cell surface integrin expression after treatment with platelet-derived growth factor (PDGF)-AA, PDGF-AB, or PDGF BB. Each isoform of PDGF produced a significant decrease in the level of alpha 1 present on the cell surface and an increase in the level of alpha 5. Furthermore, PDGF-BB produced a corresponding decrease in alpha 1 mRNA and an increase in alpha 5 mRNA. In contrast, treatment with three inflammatory cytokines, IL-1 beta, TNF-alpha, and IFN-gamma, produced clear increases in the levels of alpha 1 and alpha 5 present on the cell surface. Our observations suggest that the differential effects of PDGF and inflammatory cytokines may be part of the mechanism regulating the expression of alpha 1 and alpha 5 integrins by dermal fibroblasts during wound repair.