Prostaglandin I1 analogues,SM-10902 and SM-10906, affect human keratinocytes and fibroblasts in vitro in a manner similar to PGE1: therapeutic potential for wound healing

The newly synthesized prostaglandin (PG) I₁ analogues, SM-10902 and SM-10906, were compared with PGE₁ in terms of their biological effects on cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) in order to evaluate their therapeutic potential for cutaneous wound healing. The PGI₁ analogues had a direct effect on cell proliferation of HDFs as did PGE₁, but inibited cell growth of NHKs in contrast to the stimulatory effect observed with PGE₁. In contrast to NHKs stimulated with PGI₁ analogues, which exhibited low levels of adenosine 3,5-cyclic monophosphate (cAMP). HDFs stimulated with these analogues responded in a dose-dependent manner with extremely high levels of cAMP. Conditioned media (CM) derived from media in which HDFs had been incubated with both the PGI₁ analogues promoted NHK proliferation. HDF production of interleukin (IL)-6 increased in response to the PGI₁ 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 PGI₁ analogues.