Involvement of reactive oxygen species, protein kinase C, and tyrosine kinase in prostaglandin E2 production in Balb/c 3T3 mouse fibroblast cells by quinolone phototoxicity

We examined the effect of an antioxidant and protein kinase inhibitors on prostaglandin E-2 (PGE(2)) release from Balb/c 3T3 mouse fibroblast cells induced by quinolone phototoxicity. Simultaneous administration of sparfloxacin (SPFX) or lomefloxacin (LFLX) at 12.5 to 100 mu M and ultraviolet-A (UVA) irradiation for 10 min markedly elevated PGE(2) concentration in the incubation medium, whereas levofloxacin (LVFX) at concentrations up to 100 mu M and UVA irradiation did not increase PGE(2) concentration. Pretreatment with 100 mu M pyrrolidine dithiocarbamate (PDTC), an antioxidant, or 1 mu M calphostin C, a selective inhibitor of protein kinase C (PKC), completely inhibited the elevation of PGE(2) in the 24-h incubation medium; pretreatment with 10 mu M H7, a cyclic nucleotide-dependent protein kinase, and PKC or 1 mu M herbimycin A, a tyrosine kinase inhibitor, inhibited the PGE(2) elevation by 29 to 39%. Conversely, 25 nM staurosporine significantly augmented the PGE(2) elevation by quinolones plus UVA. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) were not detected in the incubation medium of 3T3 cells after quinolone plus UVA? corresponding to the lack of effect of antibodies against IL-1 alpha, IL-1 beta, and TNF alpha on PGE(2) release from 3T3 cells. These results suggest that PGE(2) production in 3T3 cells by quinolone phototoxicity is modulated by reactive oxygen species, PKC, and tyrosine kinase, but not by IL-1 or TNF alpha.