Increased cyclic AMP levels enhance IL-1 alpha and IL-1 beta mRNA expression and protein production in human myelomonocytic cell lines and monocytes.
The effects of increasing intracellular cAMP levels on IL-1 alpha and IL-1 beta mRNA expression and IL-1 production in human monocytes and nonlymphoid hematopoietic cell lines were examined. Peripheral monocytes and myelomonocytic cell lines could be stimulated by LPS or phorbol myristate acetate (PMA) to express IL-1 mRNA. Dibutyryl cAMP, 8-bromo-cAMP, forskolin, cholera toxin, PGE1, and PGE2 synergized with PMA or LPS to increase the accumulation in cell lines of IL-1 alpha mRNA by up to 50-fold and that of IL-1 beta mRNA by 10- to 20-fold compared to LPS or PMA alone. This increase in IL-1 alpha and IL-1 beta mRNA accumulation was more modest in monocytes. The synergistic stimulation was due to enhanced IL-1 gene transcription rate rather than increased IL-1 mRNA stability. Despite this marked increase in IL-1 mRNA accumulation, IL-1 protein synthesis in these cells was increased by only twofold. Thus, IL-1 synthesis in monocytes and myelomonocytic cell lines is under stringent translational control.
Sung
S S
SS
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Walters
J A
JA
D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate