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Altered expression of interleukin‐1 receptor antagonist in different stages of mouse skin carcinogenesis
Author(s) -
La Eunhye,
Muga Stephanie J.,
Locniskar Mary F.,
Fischer Susan M.
Publication year - 1999
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/(sici)1098-2744(199904)24:4<276::aid-mc5>3.0.co;2-#
Subject(s) - biology , 12 o tetradecanoylphorbol 13 acetate , microbiology and biotechnology , interleukin , interleukin 1 receptor antagonist , cell culture , carcinogenesis , papilloma , messenger rna , receptor antagonist , cancer research , receptor , cytokine , pathology , antagonist , immunology , signal transduction , cancer , biochemistry , phorbol ester , genetics , protein kinase c , medicine , gene
Interleukin‐1 receptor antagonist (IL‐1Ra) is an endogenous inhibitor of interleukin‐1. The expression of IL‐1Ra and interleukin‐1α ( IL‐1α ) was measured in murine epidermis after treatment with tumor promoters and in tumor cell lines. A single treatment with three different tumor promoters (12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA), anthralin, and thapsigargin) induced IL‐1Ra mRNA with different kinetics in mouse skin. The expression of IL‐1Ra mRNA also was induced by TPA and IL‐1α in a dose‐related and time‐dependent manner in cultured mouse keratinocytes. Expression of IL‐1Ra mRNA peaked 6 h after treatment. Both IL‐1Ra and IL‐1α protein and IL‐1Ra and IL‐1α mRNA were measured in various keratinocyte tumor cell lines (C50, MT1/2, HEL30, JWF2, CH72, and BPCC2). The expression of IL‐1α was increased in papilloma and squamous cell carcinoma cell lines. IL‐1Ra protein also was increased in nontumorigenic and papilloma cell lines; however, the expression was dramatically reduced in some carcinoma cell lines. Finally, we detected IL‐1α and IL‐1Ra protein in mouse skin tumors by western blot analysis, and localization was assessed by immunohistochemical analysis. Positive staining for both IL‐1α and IL‐1Ra was observed in the cytoplasm and was most prominent in the suprabasal layer. Although IL‐1Ra protein increased in papillomas and carcinomas, IL‐1α protein was not significantly increased above basal level in most tumors. Mol. Carcinog. 24:276–286, 1999. © 1999 Wiley‐Liss, Inc.