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Interleukin‐1α gene expression and localization of interleukin‐1α protein during tumor promotion
Author(s) -
Oberyszyn Tatiana M.,
Sabourin Carol L. K.,
Bijur Gautam N.,
Oberyszyn Andrew S.,
Boros Laszlo G.,
Robertson Fredika M.
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940070406
Subject(s) - dmba , epidermis (zoology) , biology , microbiology and biotechnology , endocrinology , alpha (finance) , dermis , medicine , tumor promotion , gene expression , tetradecanoylphorbol acetate , 12 o tetradecanoylphorbol 13 acetate , gene , biochemistry , phosphorylation , carcinogenesis , anatomy , phorbol ester , protein kinase c , construct validity , nursing , patient satisfaction
Treatment of the dorsal epidermis of SENCAR mice with 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) induced a time‐ and dose‐dependent stimulation of interleukin‐1α (IL‐1α) gene expression. Levels of IL‐1α mRNA were elevated as early as 15 min and peaked at 3–4 h after a single application of TPA (2 μg or 10 μg). IL‐1α gene expression increased in epidermal tissue isolated from SENCAR mice at 1, 3, 6, 10, 16, and 22 wk after a single treatment with 10 nmol 7,12‐dimethylbenz[ a ]anthracene (DMBA) and subsequent twice‐weekly application of 2 μg TPA. IL‐1α‐immunoreactive protein was specifically localized within suprabasal keratinocytes in cutaneous tissue isolated from mice treated with DMBA‐TPA for 1–22 wk and in nonproliferating cells located within papilloma tissue isolated from SENCAR mice at 22 wk after initiation and promotion. Basal cells within hyperplastic epidermis did not produce IL‐1α‐immunoreactive protein. DMBA treatment alone did not induce IL‐1α gene expression. Injection of IL‐1α‐specific antibodies (50 μg) into SENCAR mice via the tail vein 2 h before treatment with TPA (2 μg or 10 μg) significantly ( P < 0.05) inhibited the skin thickening usually observed 24 h after treatment with TPA. Autoradiography studies showed that injection of anti—IL‐1α antibodies inhibited incorporation of [methyl‐ 3 H]thymidine by keratinocytes within the epidermis and by cells within hair follicles. It also inhibited neutrophil infiltration into the dermis, which usually results from topical application of TPA. These data suggest that IL‐1α is a pivotal cytokine produced by specific subpopulations of epidermal keratinocytes and that IL‐1α primarily regulates the epidermal proliferative response of a distinctly separate population of keratinocytes after topical exposure of murine epidermis to TPA and secondarily modulates neutrophil migration into the dermis. Consequently, manipulation of IL‐1α may be a way to attenuate or abrogate the cutaneous response to TPA by altering keratinocyte proliferation, the resultant hyperplasia, and a portion of the inflammatory response characterized by dermal infiltration of neutrophils.