title: Modulation of keratinocyte proliferation in vitro by endogenous prostaglandin synthesis.
abstract: To understand the relationship between the proliferation of epidermis and its arachidonic acid metabolism, we studied human keratinocytes grown in vitro at confluent or nonconfluent densities. Keratinocyte cultures incubated with [14C]arachidonic acid synthesized prostaglandin (PG)E2 PGD2, PGF2 alpha, and small quantities of 6-keto-F1 alpha. Nonconfluent cultures, however, synthesized fourfold more PGE2 than did confluent cultures. When proliferation was studied using [3H]thymidine incorporation into DNA, it was found that this increased synthesis of PGE2 was accompanied by a fourfold increase in the rate of proliferation. When PGE2 synthesis was inhibited by indomethacin, the rate of proliferation of nonconfluent cultures was decreased 40%, while the rate of proliferation of confluent cultures was unchanged. Addition of 1 ng/ml of PGE2, but not PGF2 alpha, PGD2, or a stable analog of PGI2 to the indomethacin-treated nonconfluent cultures restored the initial rate of proliferation. These results suggest that PGE2 is a growth-promoting autocoid for epidermis. The synthesis of PGE2 by epidermis may be enhanced in wound healing and disease states where epidermal continuity is disrupted.
authors.forename: A P
authors.initials: AP
authors.lastname: Pentland
authors.forename: P
authors.initials: P
authors.lastname: Needleman
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis* / Q000502:physiology; D011458:Prostaglandins E / Q000096:biosynthesis / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D004247:DNA; D015232:Dinoprostone; D013936:Thymidine; D007213:Indomethacin