A Possible Role of Prostaglandins in PUVA-Induced Inflammation: Implication by Organ Cultured Skin

Abstract

The role of arachidonate metabolites in UV-induced inflammation was analyzed by measuring the amounts of prostaglandins or leukotrienes released into a culture medium in the organ culture of biopsied guinea pig skin following UV exposure. Increased concentrations of prostaglandin E2, F2 alpha, and 6-oxo-F1 alpha were found in the medium subjected to UVB radiation followed by 24 h incubation in the organ culture, compared to medium from non-exposed skin, whereas LTC4 was at an undetectable level in both. This release occurred in UVB dose-dependent fashion and was completely inhibited by the addition of indomethacin to the medium. Exposure to monochromatic UV light of 250, 300, and 350 nm released prostaglandin E2, F2 alpha, and 6-oxo-F1 alpha, in increasing order of 250, 300, and 350 nm, but not LTC4. This order of amount released almost paralleled the intensity of inflammation that occurred with each wavelength. Exposure of skin to UVA following intraperitoneal injection of 8-methoxypsoralen (PUVA) was also found to stimulate the synthesis of prostaglandin E2 in UVA dose-dependent fashion, and the stimulation through an increasing dose of UVA occurred more significantly than UVB exposure. The time course of prostaglandin release following UVB and PUVA exposures was found to have a pattern similar to their dynamics in association with erythema and edema, conditions which could be significantly diminished by the topical application of indomethacin. The present studies demonstrate that prostaglandins play an important role in the production of inflammation by UVB as well as UVA and PUVA.