Proteolytic enzymes have various functions in cutaneous biology. During reepithelization of skin wounds, migrating keratinocytes utilize the proteolytic urokinase system to induce the pericellular proteolysis necessary for migration. Urokinase type plasminogen activator (uPA), when bound to its specific receptor (uPAR) on keratinocytes, converts surface bound plasminogen proteolytically to plasmin, which in turn cleaves many extracellular matrix components. UPA activity is controlled by specific inhibitors like plasminogen activator inhibitor 1 (PAI-1). In addition to the complex protein interactions, the uPA system is also strongly regulated on the level of protein synthesis. UPA, uPAR, and PAI-1 are not or barely expressed in normal skin, but are strongly induced in migrating keratinocytes in wounds. In a systematic approach, we have analyzed the effects of cytokines and growth factors relevant in wound healing (IFN-γ, TNF-α, IL-1, IL-6, IL-10, IL-12, TGF-β, TGF-α, bFGF, EGF, glucocorticoids) on uPA, uPAR, and PAI-1 mRNAs expression in the permanent A431 and HaCaT keratinocyte cell lines. Total cellular RNA was prepared 4h after stimulation and analyzed by Northern blotting. Confirming previous observations, uPA mRNA was induced by TNF-α and EGF, and uPAR mRNA was induced by TGF-α and prednisolon. We also report, to our knowledge for the first time, the induction of uPAR and uPA mRNA by IL-10 and IL-12 in keratinocyte cell lines. While TGF-β strongly induced PAI-1 mRNA in HaCaT cells, the uPAR mRNA signal was decreased. Thus TGF-β had differential effects on components of the uPA system. These studies provide the basis for the analysis of transcriptional mechanisms by which components of the uPA system are controlled by cytokines and growth factors during wound healing.