IL-1alpha is a potent stimulator of keratinocyte tissue plasminogen activator expression and regulated by TGF-beta1

Archives of Dermatological Research
Xiaohua LianTian Yang

Abstract

Epidermal keratinocytes synthesize and secrete tissue-type plasminogen activator. tPA converts the inactive precursor enzyme plasminogen into the trypsin like proteinase plasmin, and is an essential component of normal wound healing. tPA is not found in normal epidermis, but in keratinocytes at the leading edge of the wound. Proteolytic activity produced by tPA is necessary for the wound epidermis to cleave fibrin from its migratory pathway. However, the factors that regulate tPA expression in keratinocytes have remained largely elusive. In the present study, we sought to determine whether the cytokine interleukin-1alpha (IL-1alpha) and its regulator transforming growth factor beta1 (TGF-beta1), which are both commonly present in skin wounds, influence tPA production in cultured murine epidermal keratinocytes. We treated the keratinocytes with IL-1alpha in the absence or presence of TGF-beta1 at various concentrations and analyzed the expression of tPA by RT-PCR, in situ hybridization, immunocytochemistry as well as immunofluorescence. We found that IL-1alpha induced mRNA and protein expression of tPA in a time and dose dependent manners. The maximal stimulation was seen at 72 h and 100 U/ml. However, treatment of keratinocytes...Continue Reading

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