Rapid enhancement of. beta. /sub 2/-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187
The expression in human fibroblasts of the ..beta../sub 2/-interferon (IFN-..beta../sub 2/) gene, which is now recognized to be identical to the gene encoding B-cell differentiation factor BSF-2, is enhanced by several cytokines that affect cell growth (tumor necrosis factor, interleukin 1, platelet-derived growth factor, and ..beta../sub 1/-interferon). The authors have examined the possibility that IFN-..beta../sub 2/ gene expressions is regulated through activation, by diacylglycerol of the protein kinase C pathway. The synthetic diacylglycerols 1,2-dioctanoylglycerol (diC/sub 8/) and 1-oleoyl-2-acetylglycerol strongly enhanced IFN-..beta../sub 2/, but not IFN-..beta../sub 1/, gene expression in human fibroblasts (FS-4 strain). An increase in IFN-..beta../sub 2/ mRNA level was detected within 15 min after addition of diC/sub 8/ (290 ..mu..M) to FS-4 cells and was maximal approximately 20 hr later. An increase in IFN-..beta../sub 2/ gene transcription was detected within 5 min of addition of diC/sub 8/, and the rate of transcription was near-maximal by 15-30 min. The enhancement of IFN-..beta../sub 2/ gene expression by diC/sub 8/, interleukin 1, or tumor necrosis factor was not prevented by H8, a preferential inhibitor of cAMP- and cGMP-dependent protein kinases, but was blocked by H7, an inhibitor of protein kinases C as well as of cyclic nucleotide-dependent protein kinases. The calcium ionophore A23187 (1-10 ..mu..M) also elicited an increase in the level of IFN-..beta../sub 2/ mRNA in FS-4 fibroblasts; appropriate combinations of A23187 and diC/sub 8/ had at least an additive effect in enhancing IFN-..beta../sub 2/ mRNA levels. These results show that protein kinase C-activating or (Ca/sup 2 +/)-elevating agents rapidly increase the expression of the IFN-..beta../sub 2/ gene in human fibroblasts.
- Research Organization:
- Rockefeller Univ., New York, NY
- OSTI ID:
- 5301246
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:12
- Country of Publication:
- United States
- Language:
- English
Similar Records
Activation of the human. beta. sub 2 -interferon/hepatocyte-stimulating factor/interleukin 6 promoter by cytokines, viruses, and second messenger agonists
Synthesis of interleukin 6 (interferon-. beta. /sub 2//B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
INTERFERON
GENE REGULATION
LYMPHOCYTES
MESSENGER-RNA
AUTORADIOGRAPHY
PHOSPHOTRANSFERASES
ENZYME INDUCTION
BIOLOGICAL PATHWAYS
FIBROBLASTS
GENES
GLYCEROL
LEUCINE
PHOSPHORUS 32
TRITIUM COMPOUNDS
URIDINE
ALCOHOLS
AMINO ACIDS
ANIMAL CELLS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ENZYMES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
LABELLED COMPOUNDS
LEUKOCYTES
LIGHT NUCLEI
LYMPHOKINES
MATERIALS
MITOGENS
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
RNA
SOMATIC CELLS
TRANSFERASES
URACILS
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550201 - Biochemistry- Tracer Techniques