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

Journal Article · Thu May 05 00:00:00 EDT 1988 · J. Biol. Chem.; (United States)

OSTI ID:6924989

Zhange, Y; Lin, J X; Vilcek, J

Interleukin 6 (IL-6; also referred to as interferon-..beta../sub 2/, 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1.

• Research Organization: New York Univ. Medical Center, NY (USA)
• OSTI ID: 6924989
• Journal Information: J. Biol. Chem.; (United States), Vol. 263:13
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMP
BIOCHEMISTRY
LYMPHOKINES
BIOSYNTHESIS
GENE REGULATION
BIOLOGICAL PATHWAYS
CELL DIFFERENTIATION
FIBROBLASTS
GROWTH
MAN
PHOSPHORUS 32
PHOSPHOTRANSFERASES
THYMIDINE
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMISTRY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ENZYMES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MITOGENS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PRIMATES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
SOMATIC CELLS
SYNTHESIS
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques