Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema.
Acute ultraviolet light B (UVB) injury is associated with dermal mast cell histamine release. The possibility that histamine-stimulated prostaglandin (PG) synthesis could be a mechanism for irradiation erythema was therefore examined using human skin explants. Explants responded to UV irradiation (120 mJ/cm2) with a fivefold increase in synthesis of prostaglandins E2, F2 alpha and 6-keto PGF1 alpha. Incubating explants with the H1 antihistamines brompheniramine (50 microM) or pyrilamine (30 microM) inhibited PG release from irradiated explants 63 +/- 4.9% (mean +/- SEM) 6 h after UV exposure. Antihistamines did not affect PG synthesis in control explants. Irradiation increased the histamine concentration in explant conditioned medium only 50% over basal values, suggesting that irradiation enhanced histamine responsiveness. Explants were therefore incubated with exogenous histamine. In irradiated explants, PG synthesis was stimulated threefold by 3 microM histamine. Unirradiated explants' PG synthesis was unaffected by histamine. Enhanced histamine sensitivity was also examined in epidermal cell cultures. In irradiated cultures, histamine sensitivity was again markedly potentiated: as little as 1 microM histamine stimulated significant PGE2 release and the response to 10-30 microM histamine was increased six to eight times compared with that of unirradiated cultures. These studies demonstrate that endogenous histamine stimulates PG synthesis in human skin after UV injury by potentiation of histamine-induced prostaglandin release. Potentiated agonist responses induced by UV exposure may contribute to the effects of UVB irradiation injury and in particular to irradiation erythema.
Washington University School of Medicine, Department of Medicine, St. Louis, Missouri 63110.
A P
AP
Pentland
M
M
Mahoney
S C
SC
Jacobs
M J
MJ
Holtzman
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001977:Brompheniramine / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D015777:Eicosanoids / Q000378:metabolism; D004817:Epidermis / Q000502:physiology; D004890:Erythema / Q000503:physiopathology*; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000502:physiology / Q000528:radiation effects; D011453:Prostaglandins / Q000096:biosynthesis*; D011738:Pyrilamine / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D013997:Time Factors; D014466:Ultraviolet Rays
D001095:Arachidonic Acids; D015777:Eicosanoids; D011453:Prostaglandins; D016718:Arachidonic Acid; D002927:Cimetidine; D006632:Histamine; D003513:Cycloheximide; D001977:Brompheniramine; D011738:Pyrilamine; D015232:Dinoprostone