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 inhibited 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.
D000527:Alprostadil / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*
D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; C086699:SM 10906; C086698:SM 10902; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil