The mast cell products histamine and serotonin stimulate and TNF-α inhibits the proliferation of murine epidermal keratinocytes in situ

To better characterize the proposed growth modulatory functions of mast cells and their products in the regulation of epidermal homeostasis, we have assessed keratinocyte proliferation by incorporation of [³H]thymidine in murine skin organ cultures after incubation with different concentrations of histamine, serotonin or TNF-alpha. Both histamine and serotonin significantly stimulate the proliferation of keratinocytes as compared to controls (P < 0.001), reaching maxima within a range from micro- to nanomolar concentrations. Even at subnanomolar concentration, TNF-alpha significantly inhibits the incorporation of labelled thyroidine by epidermal keratinocytes in murine skin organ culture (P < 0.001). These observations support the concept of mast cell products as modulators of keratinocyte proliferation, and suggest a role for mast cells in the regulation of epidermal tissue turnover under physiological conditions.