Abstract
CD14, a glycoprotein that binds bacterial lipopolysaccharide, plays a critical role in the inflammatory response to infection by gram-negative bacteria. Studies were undertaken to determine whether cyclic adenosine monophosphate (cAMP) regulates CD14 expression in macrophages. Incubation of RAW 264.7 cells with 8-Br-cAMP resulted in a significant increase in steady-state CD14 mRNA levels. The increase in mRNA levels was also associated with both cell-associated and soluble CD14 protein. H89 completely blocked the 8-Br-cAMP-induced CD14 mRNA up-regulation. There was no change in CD 14 mRNA half-life in the presence of 8-Br-cAMP. The CD14 gene transcription rate was increased about twofold after exposure to 8-Br-cAMP. cAMP-dependent increases in CD14 mRNA were also observed in rat peritoneal macrophages, demonstrating that this is an authentic response of mature macrophages. This study provides evidence that cAMP and protein kinase A are important regulators of CD14 expression in macrophages.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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8-Bromo Cyclic Adenosine Monophosphate / metabolism
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Cell Line
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Cyclic AMP / metabolism*
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Gene Expression
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Gene Expression Regulation* / drug effects
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Lipopolysaccharide Receptors / biosynthesis
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Lipopolysaccharide Receptors / genetics*
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism*
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / metabolism*
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Male
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Mice
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Phosphodiesterase Inhibitors / pharmacology
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Rats
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Rats, Sprague-Dawley
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Solubility
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Transcription, Genetic* / drug effects
Substances
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Lipopolysaccharide Receptors
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Phosphodiesterase Inhibitors
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8-Bromo Cyclic Adenosine Monophosphate
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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1-Methyl-3-isobutylxanthine