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Interleukin‐1α mediates phorbol ester‐induced inflammation and epidermal hyperplasia
Author(s) -
Lee Wha Young,
Lockniskar Mary F.,
Fischer Susan M.
Publication year - 1994
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.8.13.7926375
Subject(s) - hyperplasia , inflammation , tetradecanoylphorbol acetate , chemistry , 12 o tetradecanoylphorbol 13 acetate , cytokine , interleukin , epidermis (zoology) , phorbol , tumor promotion , interleukin 6 , infiltration (hvac) , vascular permeability , endocrinology , phorbol ester , immunology , carcinogenesis , medicine , protein kinase c , biochemistry , signal transduction , anatomy , gene , physics , thermodynamics
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) ‐la, in the epidermis of SENCAR mice. The goal of this study was to investigate the role of IL‐1α in several TPA‐induced responses in skin. Topical application of TPA (1 μg) enhanced the production of immunoreactive IL‐1α protein, primarily associated with the suprabasal keratinocytes. IL‐1α intradermally injected in the dorsal surface significantly increased ( P < 0.001) vascular permeability at low concentrations (1‐1000 μU) 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‐1α antibody (25‐75 μg). Furthermore, injected anti‐IL‐1α antibody significantly reduced ( P < 0.001) TPA‐induced inflammatory cell infiltration and epidermal hyperplasia. This study suggests that IL‐1α directly or indirectly mediates the inflammatory and hyperplastic responses elicited by topical treatment with TPA.—Lee, W. Y., Lockniskar, M. F., Fischer, S. M. Interleukin‐la mediates phorbol ester‐induced inflammation and epidermal hyperplasia. FASEB J. 8: 1081‐1087; 1994.