Regulation of Interleukin 3 mRNA Expression in Mast Cells Occurs at the Posttranscriptional Level and is Mediated by Calcium Ions

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 2; pp. 777 - 781
• Main Authors: Wodnar-Filipowicz, Aleksandra, Moroni, Christoph
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1990; National Acad Sciences
• Subjects: ACTINOMYCIN; ALKALINE EARTH METAL COMPOUNDS; ANIMAL CELLS; ANIMALS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIGENS; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; AUTORADIOGRAPHY; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOSYNTHESIS; BONE MARROW CELLS; Calcimycin - pharmacology; Calcium; Calcium - pharmacology; CALCIUM COMPOUNDS; CARCINOGENS; CATIONS; Cell Line; Cell lines; Cell nucleus; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cells, Cultured; CHARGED PARTICLES; Colony-Stimulating Factors - genetics; CONNECTIVE TISSUE CELLS; Cycloheximide - pharmacology; Dactinomycin - pharmacology; DAYS LIVING RADIOISOTOPES; DNA HYBRIDIZATION; DRUGS; ELECTROPHORESIS; ESTERS; Fundamental and applied biological sciences. Psychology; Gene expression; Gene expression regulation; Gene Expression Regulation - drug effects; GENE REGULATION; Genes; Genes - drug effects; GLOBULINS; Granulocyte-Macrophage Colony-Stimulating Factor; GROWTH FACTORS; Growth Substances - genetics; HYBRIDIZATION; IMMUNOGLOBULINS; Interleukin-3 - genetics; IONS; ISOTOPES; LIGHT NUCLEI; LYMPHOKINES; MAMMALS; MAST CELLS; Mast Cells - drug effects; Mast Cells - immunology; MEMBRANE PROTEINS; MESSENGER-RNA; MICE; MITOGENS; Molecular and cellular biology; Molecular genetics; Myeloid cells; NUCLEI; NUCLEIC ACIDS; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; PHORBOL ESTERS; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; Protein Kinase C - metabolism; PROTEINS; RADIOISOTOPES; RECEPTORS; RNA; RNA Processing, Post-Transcriptional - drug effects; RNA, Messenger - biosynthesis; RNA, Messenger - drug effects; RNA, Messenger - genetics; RODENTS; Signal Transduction - drug effects; SOMATIC CELLS; SYNTHESIS; T lymphocytes; Tetradecanoylphorbol Acetate - pharmacology; TRANSCRIPTION; Transcription, Genetic - drug effects; VERTEBRATES 550201 > Biochemistry > Tracer Techniques; Calcium; Rodentia; Cytokine; Gene expression; Signal transduction; Vertebrata; Regulation(control); Mammalia; Cell line; Mouse; Interleukin 3; Mast cell; Ionophore; Granulocyte macrophage colony stimulating factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.2.777

Interleukin 3 (IL-3) is transiently produced by murine bone marrow-derived mast cells in response to antigen stimulation of the high-affinity immunoglobulin E receptors. We have studied the postreceptor signaling pathways involved in regulating expression of the IL-3 gene in the murine mast cell line PB-3c. Large amounts of IL-3 mRNA accumulated after exposure of cells to calcium ionophore A23187, a reagent that increases intracellular Ca2+. Phorbol 12-myristate 13-acetate, which stimulates protein kinase C, did not induce IL-3 mRNA accumulation, although it did potentiate the effect of A23187. Nuclear run-on analysis showed that the IL-3 gene is constitutively transcribed in unstimulated cells and that treatment with A23187 and/or phorbol ester has no influence on its transcription rate. The effect of A23187 was found to be due to stabilization of the IL-3 mRNA. In cells maintained in the presence of A23187 the IL-3 mRNA was stable during 3 hr of incubation with actinomycin D, whereas removal of A23187 under the same conditions resulted in rapid degradation of the mRNA. These results indicate that control of expression of the IL-3 gene in mast cells is primarily at the posttranscriptional level and that the Ca2+-dependent signal-transduction pathway plays an important role in this process. Synthesis of granulocyte/macrophage colony-stimulating factor mRNA in response to A23187 and phorbol ester was found to be subject to both transcriptional and posttranscriptional regulation.