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Elevation of Cyclic AMP Levels in Astrocytes Antagonizes Cytokine‐Induced Adhesion Molecule Expression
Author(s) -
Ballestas Mary E.,
Benveniste Etty N.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69041438.x
Subject(s) - forskolin , rolipram , intercellular adhesion molecule 1 , cell adhesion molecule , cholera toxin , tumor necrosis factor alpha , cytokine , biology , icam 1 , vcam 1 , endocrinology , microbiology and biotechnology , medicine , signal transduction , phosphodiesterase , chemistry , biochemistry , immunology , enzyme , stimulation
We have examined the effect of elevating cyclic AMP levels on cytokine‐mediated enhancement of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) gene expression by astrocytes. Treatment of astrocytes with the cyclic AMP mimetic dibutyryl‐cyclic AMP, or the agonists norepinephrine, forskolin, prostaglandin E 2 , and cholera toxin alone had no effect on ICAM‐1 or VCAM‐1 mRNA gene expression. However, elevating cyclic AMP levels within the cells by these agents suppressed interleukin‐1β‐ and tumor necrosis factor‐α‐induced adhesion molecule expression at both the mRNA and protein levels. The phosphodiesterase type IV inhibitor, rolipram, was able to potentiate the inhibitory effect of forskolin on ICAM‐1 and VCAM‐1 gene expression. Inhibition of tumor necrosis factor‐α‐induced VCAM‐1 mRNA levels by forskolin was partially due to enhanced degradation of VCAM‐1 message, whereas the decay rates of tumor necrosis factor‐α‐induced ICAM‐1 message and interleukin‐1β‐induced ICAM‐1/VCAM‐1 message were not affected by forskolin treatment. These results demonstrate that the pathways used by interleukin‐1β and tumor necrosis factor‐α to induce adhesion molecule expression are antagonized by cyclic AMP‐dependent protein kinase‐mediated signaling pathways.