Leukotrienes B4, C4 and D4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Leukotrienes in psoriatic skin lesions are potent mediators of inflammation. We have studied the capacity of leukotrienes to stimulate the DNA synthesis of cultured human epidermal keratinocytes. At concentrations ranging from 10(-12) to 10(-8) M, LTB4 produced a 100% increase of DNA synthesis determined both as the incorporation of [3H] thymidine and as the labelling index. In comparison, LTB4 had no effect on the DNA synthesis of dermal fibroblast cultures. 5S,12S-LTB4 and 5S,12S-all-trans-LTB4 did not change the DNA synthesis of keratinocytes, but the effect of LTB4 was abolished in the presence of 5S,12S-all-trans HLTB4. Being less potent than LTB4 the peptidoleukotrienes (LTC4, LTD4) also stimulated keratinocyte DNA synthesis. The effect of the peptidoleukotrienes, but not of LTB4, was antagonized by FPL 55712. These results show that leukotrienes B4, C4 and D4 exert potent and stereospecific mitogenic effects on cultured human keratinocytes. The presence of these arachidonic acid metabolites in psoriatic skin lesions may be pertinent to both inflammation and aberrant epidermal growth in psoriasis.