PROSTAGLANDIN I-1 ANALOGS, SM-10902 AND SM-10906, AFFECT HUMAN KERATINOCYTES AND FIBROBLASTS IN-VITRO IN A MANNER SIMILAR TO PGE(1) - THERAPEUTIC POTENTIAL FOR WOUND-HEALING

The newly synthesized prostaglandin (PG) I-1 analogues, SM-10902 and S M-10906, were compared with PGE(1) in terms of their biological effect s on cultured normal human keratinocytes (NHKs) and human dermal fibro blasts (HDFs) in order to evaluate their therapeutic potential for cut aneous wound healing, The PGI(1) analogues had a direct effect on cell proliferation of HDFs as did PGE(1), but inibited cell growth of NHKs in contrast to the stimulatory effect observed with PGE(1). In contra st to NHKs stimulated with PGI(1) analogues, which exhibited low level s of adenosine 3,5-cyclic monophosphate (cAMP), HDFs stimulated with t hese analogues responded in a dose-dependent manner with extremely hig h levels of cAMP, Conditioned media (CM) derived from media in which H DFs had been incubated with both the PGI(1) analogues promoted NHK pro liferation, HDF production of interleukin (IL)-6 increased in response to the PGI(1) analogues, Since IL-6 was shown to promote cell growth of NHKs, enhancement of NHK proliferation by CM was thought to be due to IL-6 derived from HDFs stimulated with the PGI(1) analogues.