Interleukin-1 beta upregulates tissue-type plasminogen activator in a keratinocyte cell line (HaCaT)

Human keratinocytes synthesize and secrete tissue-type plasminogen activator (tPA). tPA converts the inactive precursor enzyme plasminogen into the trypsin-like proteinase plasmin. tPA is not found in normal epidermis, but in lesional epidermis from patients with a variety of cutaneous diseases, including psoriasis, pemphigus and pemphigoid. The presence of tPA is probably a reaction to the disease process rather than the initiating event in these etiologically and histopathologically diverse lesions. However, the factor(s) that upregulate tPA expression and secretion in keratinocytes have remained largely elusive. We sought to determine whether the inflammatory cytokine interleukin-1 beta (IL-1 beta), which is commonly present in diverse epidermal lesions, influences tPA production. Accordingly, we studied the influence of IL-1 beta on secretion of tPA by cells of the human keratinocyte cell line HaCaT. We found that IL-1 beta increased tPA secretion in these cells. Given the observation that IL-1 beta is a common proinflammatory mediator in cutaneous diseases, our findings may explain the increase in tPA in clinically and etiologically diverse inflammatory epidermal lesions.