Effects of prostaglandin E1 on human keratinocytes and dermal fibroblasts: A possible mechanism for the healing of skin ulcers

Abstract

The effects of prostaglandin E, (PGE) on cell growth, cytokine production and interaction of cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) were investigated. When NHKs were treated with PGE, directly, only a slight increase in cell growth and a transient decrease in interleukin 1 alpha (IL‐lα) secretion were observed. No IL‐6 was detected either before or after PGE, treatment. In addition, IL‐8 and transforming growth factor alpha (TGFα) production were uninfluenced by PGE. The response of HDFs to PGE, differed from that of NHKs. Following PGE₁, treatment, IL‐lα and TGFα. from HDFs remained undetectable while IL‐6 production was enhanced markedly. IL‐8 production was also slightly enhanced. Exposure of HDFs to PGE, for 96 hours significantly promoted cell proliferation. Two kinds of conditioned media (CM) were prepared by a brief feeding of HDFs with keratinocyte basic medium or Dulbecco's modified Eagle's medium supplemented with 5% PCS with or without PGE. NHKs proliferated more rapidly in CM than in corresponding basic medium. Moreover, CM prepared with PGE, treatment showed a stronger effect in promoting NHK proliferation than CM without PGE, treatment. This promoting effect was inhibited by anti‐human IL‐6 monoclonal antibody dose‐dependently. These results indicate that fibroblasts are more sensitive than keratinocytes in response to PGE, and that, upon PGE, stimulation. HDF‐derived IL‐6 may play an essential role in NHK cell proliferation which may at least partly account for the beneficial effects of PGE, in the treatment of cutaneous liberations.