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 |
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Authors: | Kohji Shimoda Michiyuki Kato |
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Institution: | (1) Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kita-kasai, Edogawa-ku, Tokyo 134, Japan, JP |
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Abstract: | We examined the effect of an antioxidant and protein kinase inhibitors on prostaglandin E2 (PGE2) 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 μ M and ultraviolet-A (UVA) irradiation for 10 min markedly elevated PGE2 concentration in the incubation medium, whereas levofloxacin (LVFX) at concentrations up to 100 μ M and UVA irradiation did
not increase PGE2 concentration. Pretreatment with 100 μ M pyrrolidine dithiocarbamate (PDTC), an antioxidant, or 1 μ M calphostin C, a selective
inhibitor of protein kinase C (PKC), completely inhibited the elevation of PGE2 in the 24-h incubation medium; pre-treatment with 10 μ M H7, a cyclic nucleotide-dependent protein kinase, and PKC or 1 μ
M herbimycin A, a tyrosine kinase inhibitor, inhibited the PGE2 elevation by 29 to 39%. Conversely, 25 nM staurosporine significantly augmented the PGE2 elevation by quinolones plus UVA. Interleukin-1β (IL-1β ) and tumor necrosis factor α (TNFα ) were not detected in the incubation
medium of 3T3 cells after quinolone plus UVA, corresponding to the lack of effect of antibodies against IL-1α , IL-1β , and
TNFα on PGE2 release from 3T3 cells. These results suggest that PGE2 production in 3T3 cells by quinolone phototoxicity is modulated by reactive oxygen species, PKC, and tyrosine kinase, but
not by IL-1 or TNFα .
Received: 23 September 1997 / Accepted: 1 December 1997 |
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Keywords: | Quinolone Phototoxicity Fibroblasts Prostaglandin E2 |
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