Upregulation of Cell-Surface-Associated Plasminogen Activation in Cultured Keratinocytes by Interleukin-1βand Tumor Necrosis Factor-α

Autor: Bechtel, Michael J., Reinartz, Jeannette, Rox, Jutta M., Inndorf, Stefan, Schaefer, Birgit M., Kramer, Michael D.
Zdroj: Experimental Cell Research; March 1996, Vol. 223 Issue: 2 p395-404, 10p
Abstrakt: Keratinocytes synthesize and secrete urokinase-type plasminogen activator (uPA) which is bound in an autocrine manner to a specific receptor (uPA-R) at the keratinocyte surface. Plasminogen that is also bound to specific membrane binding sites is readily activated by uPA-R-bound uPA. Thus, plasmin is provided for proteolysis of pericellular glycoproteins. The expression of uPA and the uPA-R is confined to migrating keratinocytes during epidermal wound healing, rather than to keratinocytes of the normal epidermis. The regulatory factors of uPA/uPA-R expression in keratinocytes remained largely elusive. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β), are present in epidermal wounds. We have therefore tested IL-1β and TNF-α for their influence on surface-associated plasminogen activation in a human keratinocyte cell line (HaCaT) as well as in primary cultures of normal human epidermal keratinocytes. Both cytokines induced the secretion of uPA into the culture supernatants and a concomitant increase in uPA activity as well as in uPA and uPA-R antigen at the cell surface. The increase was preceded by an increase in specific mRNA. The induction was accompanied by an accelerated uPA-dependent and plasmin-mediated detachment of HaCaT cells from the culture substratum. Taken together, the proinflammatory cytokines IL-1β and TNF-α induced a coordinated increase in uPA and uPA-R as well as increased pericellular plasmin-mediated proteolysis in human epidermal keratinocytes. This function might be an element of the molecular cell biological events during epidermal wound healing.
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