Inhibition of 12-O-Tetradecanoylphorbol-13-Acetate and Other Skin Tumor-Promoter-Caused Induction of Epidermal Interleukin-1α mRNA and Protein Expression in SENCAR Mice by Green Tea Polyphenols

Katiyar, Santosh K.; Rupp, Cornelia O.; Korman, Neil J.; Agarwal, Rajesh; Mukhtar, Hasan
September 1995
Journal of Investigative Dermatology;Sep95, Vol. 105 Issue 3, p394
Academic Journal
Recent studies have shown that topical application of the tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA) to murine skin results in increased expression of the highly inflammatory cytokine interleukin (IL)-1α in the epidermis. This has led to the suggestion that IL-1α directly or indirectly mediates the inflammatory and hyperplastic responses elicited by TPA and possibly by other skin tumor promoters. In the current study, we investigated the effect of skin application of a polyphenolic fraction isolated from green tea (GTP) to SENCAR mice on skin tumor- promoter-caused induction of cutaneous edema and hyperplasia, and IL-1α mRNA expression. Pretreatment of the skin with GTP 30 mm before that of anthralin, benzoyl peroxide, mezerein, and TPA resulted in a significant (p < 0.05) inhibition of cutaneous edema and epidermal hyperplasia caused by each of these tumor promoters. Northern blot analysis indicated that topical application of TPA, anthralin, mezerein, or benzoyl peroxide to SENCAR mice resulted in an increased expression of epidermal IL-1α mRNA. Pretreatment of the skin with GTP or individual epicatechin derivatives (ECDs) present therein, 30 mm before that of TPA, resulted in a significant inhibition of enhanced expression of epidermal IL-1α mRNA caused by skin application of TPA. These inhibitory effects were found to be dependent on the dose of GTP. Among four epicatechin derivatives present in GTP, (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate were more effective than (-)-epigallocatechin and (-)-epicatechin in affording this inhibition. Preapplication of GTP was also found to afford inhibition against anthralin-, benzoyl peroxide-, and mezerein-caused increased expression of epidennal IL-1α mRNA and protein.


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