Leukotrienes B 4 , C 4 and D 4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Abstract

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, LTB 4 produced a 100% increase of DNA synthesis determined both as the incorporation of [ 3 H] thymidine and as the labelling index. In comparison, LTB 4 had no effect on the DNA synthesis of dermal fibroblast cultures. 5S, 12S-LTB 4 and 5S, 12S-all-trans-LTB 4 did not change the DNA synthesis of keratinocytes, but the effect of LTB 4 was abolished in the presence of 5S, 12S-all- trans HLTB 4 . Being less potent than LTB 4 the peptidoleukotrienes (LTC 4 , LTD 4 ) also stimulated keratinocyte DNA synthesis. The effect of the peptidoleukotrienes, but not of LTB 4 , was antagonized by EPL 55712. These results show that leukotrienes B 4 , C 4 and D 4 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.