Antagonistic effects of calcium ionophores and phorbol esters on T cell receptor mRNA levels in human thymocytes

• Published in: The Journal of immunology (1950) Vol. 140; no. 2; pp. 361 - 366
• Main Authors: Martinez-Valdez, H, Doherty, PJ, Thompson, E, Benedict, SH, Gelfand, EW, Cohen, A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.01.1988; American Association of Immunologists
• Subjects: Biological and medical sciences; Calcium - metabolism; Enzyme Activation - drug effects; Ethers - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - drug effects; Humans; Immunobiology; Ionomycin; Ionophores - pharmacology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Nucleic Acid Hybridization; Protein Kinase C - metabolism; Receptors, Antigen, T-Cell - analysis; Receptors, Antigen, T-Cell - drug effects; Receptors, Antigen, T-Cell - genetics; RNA, Messenger - antagonists & inhibitors; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.140.2.361

Levels of mRNA of the T cell antigen receptors (TcR) in human thymocytes are differentially regulated in response to distinct intracellular signals. Activation of protein kinase C by the phorbol ester, tetradecanoyl phorbol acetate or other phorbol esters increases the levels of the alpha and beta T cell receptor (TcR-alpha, TcR-beta) mRNA, whereas an increase in cytosolic free Ca2+, induced by ionomycin or other Ca2+ ionophores, results in a decrease of alpha and beta TcR mRNA levels. In contrast, ionomycin increases the expression TcR-gamma mRNA whereas tetradecanoyl phorbol acetate prevents this induction. Our results suggest the existence of two opposing intracellular pathways that control expression of TcR-alpha and TcR-beta mRNA levels, on the one hand and TcR-gamma mRNA, on the other. These results provide the first evidence for antagonistic actions of protein kinase C and cytosolic-free Ca2+ on gene expression.