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INHIBITORY EFFECT OF 8‐METHOXYPSORALEN PLUS ULTRAVIOLET‐A ON INTERLEUKIN‐1 PRODUCTION BY MURINE KERATINOCYTES

We report the effects of 8‐methoxypsoralen (8‐MOP) plus ultraviolet‐A (UV‐A) irradiation on interleukin‐1 (IL‐1) production by murine epidermal keratinocytes, correlating its effect on IL‐1 with cell viability, DNA synthesis, and 8‐MOP‐DNA photoadduct formation. Freshly isolated murine keratinocytes were treated with various doses of 8‐MOP (5–100 ng/mL; incubation time, 30 min) plus 1 J/cm2 UV‐A and cultured for 1–3 days. The IL‐1/epidermal cell‐derived thymocyte‐activating factor (ETAF) activity in both supernatant and cell extract was reduced proportionately with increasing doses of 8‐MOP/UV‐A. Interleukin‐1 inhibitors induced by 8‐MOP plus UV‐A were not detected in either supernatant or cell extract. A clear reduction of the IL‐1 production was induced by the treatment as low as 15 ng/mL 8‐MOP plus 1 J/cm2 UV‐A, which led to the formation of 0.52 8‐MOP photoadducts per million DNA bases and affected neither cell viability nor DNA synthesis of the treated cells. Cells treated with 100 ng/mL 8‐MOP and 1 J/cm2 UV‐A exhibited 57% suppression of IL‐1 production in both 2‐ and 3‐day culture samples. This treatment resulted in the formation of 3.8 photoadducts per million bases as well as significant abrogation of DNA synthesis although cell viability was unchanged. These observations provide some insights into the phototoxicity mechanisms of 8‐MOP and the effect of PUVA therapy on the cytokine regulation in keratinocytes.