Phorbol ester, ultraviolet light and oxidative stress induced inflammation and up-regulation of pro-inflammatory cytokines in mouse ears

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12-O-Tetradecanoylphorbol-13-acetate (TPA), ultraviolet light (UV) and benzoyl peroxide (oxidative stress) can activate the innate immune response in the mouse ear model and induce inflammation and increase the expression of pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) in ears of CD-1 mice. A single topical application of TPA (0.2 –2 nmol) to the ears of CD-1 mice induced a dose- and time-dependant ear edema and formation of over-expression of pro-inflammatory cytokines, IL-1 beta and IL-6 in the ears. Both ears of CD-1 mice were treated topically with acetone or TPA (0.8 –1.0 nmol) in acetone once a day for 4 days. The mice were sacrificed at 6 hours after the last dose of TPA. This treatment induced ear inflammation, over-expression of IL-1 beta and IL-6 as well as increased formation of the arachidonic acid metabolites PGE2 and LTB4 in a dose-dependant manner. Topical application of benzoyl peroxide (2 mg) or irradiation with UV light (180 mJ/cm2) to CD-1 mice once a day for 4 days induced ear inflammation and increased over-expression of IL-1 beta and IL-6 in ears. Topical application of antioxidant nutraceuticals (-)-epigallocatechin gallate (EGCG), theaflavin, theaflavin-3, 3′-digallate, curcumin, or caffeic acid phenethyl ester at 20 –30 min before topical application of TPA (0.8 –1.0 nmol) once a day for 4 days inhibited TPA-induced inflammation, over-expression of IL-1 beta and IL-6 as well as the formation of PGE2 and LTB4 in mouse ears (Supported by the NJ State Commission on Science and Technology).