Signal transduction pathway(s) involved in phorbol ester and autocrine induction of interleukin-1 alpha mRNA in murine keratinocytes

• Published in: The Journal of biological chemistry 1994-07, Vol.269 (27), p.17971-17980
• Main Authors: Lee, W Y, Butler, A P, Locniskar, M F, Fischer, S M
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cells, Cultured; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genistein; Interleukin-1 - genetics; Interleukin-1 - metabolism; Isoflavones - pharmacology; Isoquinolines - pharmacology; Keratinocytes - cytology; Keratinocytes - metabolism; Mice; Mitogen-Activated Protein Kinase 1; Molecular and cellular biology; Molecular genetics; NF-kappa B - metabolism; Piperazines - pharmacology; Protein hormones. Growth factors. Cytokines; Protein Kinase C - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-jun - metabolism; RNA, Messenger - biosynthesis; Signal Transduction; Tetradecanoylphorbol Acetate - pharmacology; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)32405-5

We investigated the signal transduction pathways leading to the 12-O-tetradecanoylphorbol-13-acetate (TPA)- and interleukin-1 alpha (IL-1)-induced IL-1 alpha mRNA in mouse keratinocytes. Induction of IL-1 alpha mRNA by TPA or IL-1 alpha was followed by increases in cell-associated IL-1 alpha protein measured by enzyme-linked immunosorbent assay. Although protein kinase C (PKC) was involved in TPA-induced IL-1 alpha mRNA, down-regulation of PKC did not block the induction of this gene by TPA. The autocrine induction of IL-1 alpha was not mediated through PKC or cAMP. IL-1 alpha did activate mitogen-activated protein kinase. Genistein, a tyrosine kinase inhibitor, blocked both IL-1 alpha-induced mitogen-activated protein kinase activation as well as IL-1 alpha mRNA expression. Genistein, at an unsaturating dose, plus a serine/threonine kinase inhibitor, H7, completely blocked the autocrine induction of IL-1 alpha suggesting that expression of this gene is regulated by tyrosine kinase(s) in combination or independently with serine/threonine kinase(s). In addition, both TPA and IL-1 alpha caused increases not only in the phosphorylation of c-Jun and c-Fos protein but also in the transactivating activity of AP-1 nuclear transcription factor. Neither TPA nor IL-1 alpha induced NF-kappa B binding activity, as assessed by electrophoretic mobility shift analysis. This study suggests that the activation of AP-1 may be a common event through which TPA and IL-1 alpha induce IL-1 alpha mRNA.