Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases

Journal Article · Wed Mar 01 00:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.5.1657· OSTI ID:5085081

Raz, A; Wyche, A; Needleman, P ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MO (USA)

The authors have recently shown that the synthesis of cyclooxygenase in human dermal fibroblasts is markedly stimulated by the cytokine interleukin 1 (IL-1). They now show that the temporal sequence of the induced synthesis of PG synthase can be separated into an early transcriptional (i.e., actinomycin D inhibitable) phase and a subsequent translational (cycloheximide but not actinomycin D inhibitable) phase and that IL-1 exerts its effect during the transcriptional phase. Phorbol 12-myristate 13-acetate also stimulates synthesis of PG synthase and, together with IL-1, produces a synergistic stimulatory effect. Inhibitors of protein kinase C activation abolished the stimulatory effect of IL-1, suggesting that protein kinase C activation is a critical event in the signal-transduction sequence of the IL-1-induced increase of PG synthase synthesis. The antiinflammatory glucocorticosteroids dexamethasone and triamcinolone, but not progesterone or testosterone, were potent inhibitors of PG synthase synthesis when added during the translational phase of the synthesis sequence. The glucocorticosteroid effect was blocked by RNA and protein synthesis inhibitors. This report suggests that glucocorticosteroids exert their effect via a newly synthesized protein, causing a profound translational control of PG synthase synthesis. This novel mechanism of suppression of arachidonate metabolism is distinct from any influence of steroids on phospholipase A{sub 2} activity.

• OSTI ID: 5085081
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:5; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
GLUCOCORTICOIDS
BIOCHEMISTRY
HYDROXYLASES
PHARMACOLOGY
PHORBOL ESTERS
BIOLOGICAL EFFECTS
DOSE-RESPONSE RELATIONSHIPS
FIBROBLASTS
LYMPHOKINES
METHIONINE
PHOSPHOTRANSFERASES
PROSTAGLANDINS
SKIN
SULFUR 35
ADRENAL HORMONES
AMINO ACIDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CARCINOGENS
CHEMISTRY
CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
ESTERS
EVEN-ODD NUCLEI
GROWTH FACTORS
HYDROXY COMPOUNDS
ISOTOPES
KETONES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MITOGENS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHOSPHORUS-GROUP TRANSFERASES
PREGNANES
PROTEINS
RADIOISOTOPES
SOMATIC CELLS
STEROIDS
SULFUR ISOTOPES
TRANSFERASES
550201* - Biochemistry- Tracer Techniques