Interleukin-1 alpha mediates phorbol ester-induced inflammation and epidermal hyperplasia.
The topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to murine skin produces acute inflammatory and hyperplastic responses that have been associated with the promotion stage of skin carcinogenesis. It has been shown in a previous study that TPA induces the expression of the highly inflammatory cytokine, interleukin (IL) -1 alpha, in the epidermis of SENCAR mice. The goal of this study was to investigate the role of IL-1 alpha in several TPA-induced responses in skin. Topical application of TPA (1 microgram) enhanced the production of immunoreactive IL-1 alpha protein, primarily associated with the suprabasal keratinocytes. IL-1 alpha intradermally injected in the dorsal surface significantly increased (P < 0.001) vascular permeability at low concentrations (1-1000 microU) and increased (P < 0.001) inflammatory cell infiltration and epidermal hyperplasia at higher concentrations (10(3) U). TPA produced fourfold increases in vascular permeability as measured by Evans blue dye leakage; this effect was prevented by intradermal injection of anti-IL-1 alpha antibody (25-75 micrograms). Furthermore, injected anti-IL-1 alpha antibody significantly reduced (P < 0.001) TPA-induced inflammatory cell infiltration and epidermal hyperplasia. This study suggests that IL-1 alpha directly or indirectly mediates the inflammatory and hyperplastic responses elicited by topical treatment with TPA.
Lee
W Y
WY
Division of Pharmacology/Toxicology, College of Pharmacy, University of Texas at Austin 78712.
Lockniskar
M F
MF
Fischer
S M
SM
D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D004817:Epidermis / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D018632:Mice, Inbred SENCAR; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate
D007375:Interleukin-1; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate