No abstract

Background: Previous studies have demonstrated appreciable tumor induction in mouse skin by daily irradiation with high-power long-wavelength ultraviolet A (UVA). Object: The aim of the present study was to examine the enhancing effects of UVA on changes in mouse skin mediated by the tumor promoter 12-o-tetradecanoylphorbol-13-acetate (TPA) by measurement of ornithine decarboxylase (ODC) activity and morphometric analysis. In addition, we examined the inhibitory effects of curcumin, a component of turmeric, on these changes. Method: ODC activity in the epidermis of CD-1 mice was determined by the method of Russell and Snyder. Epidermal and dermal thickness, and the number of dermal infiltrating inflammatory cells were quantified using a computer-assisted image analyzer. Results: A combination of topical TPA application and UVA irradiation produced a greater increment of ODC activity at 4 h than TPA alone (p < 0.05). Histopathologically, TPA plus UVA tended to increase the dermal infiltrating inflammatory cells in contrast to TPA alone. Pretreatment of mice with curcumin significantly abrogated the TPA-induced changes in ODC activity and the dermal infiltrating inflammatory cells as well as the TPA plus UVA-mediated enhancement of these changes. Conclusion: Our data indicate that UVA irradiation (18.72 J/cm²) significantly enhances ODC induction at an early stage (4–6 h) after topical application of TPA, and aggravates the dermatitis elicited by TPA. Pretreatment with curcumin significantly inhibits these enhancing effects.

ABSTRACT:Bacillus Calmette-Gué rin (BCG) and lipopolysaccharide (LPS) are well known potent activators of the cell-mediated immune system and thus lead to the decreases in cytochrome P450 (P450). In this study we used interleukin (IL)-1␣/␤, IL-6, or tumor necrosis factor ␣ (TNF␣) knockout (KO) mice to investigate how each cytokine is involved in P450 down-regulation, especially CYP3A11 and 2C29. BCG (40 mg/kg) was found to reduce both CYP3A11 and 2C29 mRNAs at 24 h after treatment in IL-1␣/␤ ⌲⌷ mice in a manner similar to that seen in wild-type mice. CYP3A11 mRNA, but not CYP2C29 mRNA, was significantly decreased by BCG treatment in the TNF␣ KO mice, although the decrease was less than that of wild-type or IL-1␣/␤ KO mice. In contrast, BCG showed no significant effect on CYP3A11 and 2C29 mRNAs in IL-6 KO mice. On the other hand, LPS was able to decrease CYP3A11 and 2C29 mRNA levels in all of the cytokine KO mice and markedly increased systemic levels of TNF␣; BCG (40 mg/kg) lacked such activity. The present study has shown that IL-6 and TNF␣ are likely to be major factors involved in the down-regulation of CYP3A11 and 2C29 mRNAs in mice. In addition, there exist differences in the amount and/or kind of cytokines released by BCG or LPS, the latter being more potent than the former. This will be a possible reason for differential capability of P450 down-regulation between BCG and LPS.

No abstract