The effects of
prostaglandin E1 (
PGE1) 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
PGE1 directly, only a slight increase in cell growth and a transient decrease in
interleukin 1 alpha (IL-1 alpha) secretion were observed. No
IL-6 was detected either before or after
PGE1 treatment. In addition,
IL-8 and
transforming growth factor alpha (
TGF alpha) production were uninfluenced by
PGE1. The response of HDFs to
PGE1 differed from that of NHKs. Following
PGE1 treatment,
IL-1 alpha and
TGF alpha from HDFs remained undetectable while
IL-6 production was enhanced markedly.
IL-8 production was also slightly enhanced. Exposure of HDFs to
PGE1 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% FCS with or without
PGE1. NHKs proliferated more rapidly in CM than in corresponding basic medium. Moreover, CM prepared with
PGE1 treatment showed a stronger effect in promoting NHK proliferation than CM without
PGE1 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
PGE1 and that, upon
PGE1 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
PGE1 in the treatment of cutaneous ulcerations.