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.
Gailit
J
J
Department of Dermatology, State University of New York at Stony Brook 11794, USA.
Xu
J
J
Bueller
H
H
Clark
R A
RA
D000818:Animals; D015152:Blotting, Northern; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism*; D012867:Skin / Q000187:drug effects; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D016207:Cytokines; D005353:Fibronectins; D039222:Integrin alpha1beta1; D016023:Integrins; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen