thapsigargin and Precancerous-Conditions

Interleukin-1 receptor antagonist (IL-1Ra) is an endogenous inhibitor of interleukin-1. The expression of IL-1Ra and interleukin-1alpha (IL-1alpha) 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-1alpha 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-1alpha protein and IL-1Ra and IL-1alpha mRNA were measured in various keratinocyte tumor cell lines (C50, MT1/2, HEL30, JWF2, CH72, and BPCC2). The expression of IL-1alpha 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-1alpha and IL-1Ra protein in mouse skin tumors by western blot analysis, and localization was assessed by immunohistochemical analysis. Positive staining for both IL-1alpha 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-1alpha protein was not significantly increased above basal level in most tumors.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthralin; Blotting, Northern; Blotting, Western; Carcinogens; Carcinoma, Squamous Cell; Cell Polarity; Cytoplasm; Disease Progression; Epidermis; Gene Expression Regulation, Neoplastic; Hyperplasia; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Keratinocytes; Mice; Mice, Inbred SENCAR; Neoplasm Proteins; Papilloma; Precancerous Conditions; RNA, Messenger; RNA, Neoplasm; Sialoglycoproteins; Skin Diseases; Skin Neoplasms; Tetradecanoylphorbol Acetate; Thapsigargin; Tumor Cells, Cultured