Stimulation of Prostaglandin Production by Quinolone Phototoxicity in Balb/c 3T3 Mouse Fibroblast Cellsin Vitro

Sparfloxacin (SPFX) and levofloxacin (LVFX) with ultraviolet-A (UVA) irradiation have been reported to induce skin inflammation due to phototoxicity in Balb/c mice. We examined the production of arachidonic acid metabolites induced by quinolone phototoxicity in Balb/c 3T3 mouse fibroblast cellsin vitro.The cells were simultaneously treated with SPFX or LVFX at 1, 10, or 100 μmand UVA irradiation for 5 min (0.5 J/cm²). They were then cultured in quinolone-free medium for 24 hr, and the concentrations of prostaglandin E₂(PGE₂), 6-ketoprostaglandin F_1α(6-keto-PGF_1α), and leukotriene B₄(LTB₄) in the incubation medium were measured. Furthermore, the effect of quinolone photoproducts on the production of the inflammatory mediators and that of indomethacin on PGE₂level were also examined. Treatment with SPFX at 100 μmplus UVA irradiation markedly increased levels of PGE₂and 6-keto-PGF_1α, but not that of LTB₄. SPFX or LVFX alone at up to 100 μm, 10 μmSPFX, or 100 μmLVFX, or less plus UVA irradiation, or UVA-preirradiated quinolone up to 100 μmhad no effect. Indomethacin even at 0.1 μmcompletely inhibited the PGE₂elevation induced by 100 μmSPFX with UVA. These results suggest that PGs released from dermal fibroblasts in the simultaneous presence of quinolone and UVA could contribute in part to the development of skin inflammationin vivo.