Inhibition of lipopolysaccharide-induced IL-1 beta transcription by cyclic adenosine monophosphate in human astrocytic cells.
The response to LPS includes synthesis by monocytes of the inflammatory mediator IL-1 beta. Although the intracellular signaling pathways activated by LPS that lead to IL-1 beta production have been studied extensively in monocytes, these pathways have not been investigated in astrocytes, an important source of IL-1 beta in the central nervous system. cAMP has been implicated in LPS signaling as a positive regulator of IL-1 beta mRNA accumulation in monocytes. In this study, we demonstrate that in human astrocytes (both fetal and the astrocytoma cell line, U-373 MG), agents that elevate intracellular cAMP decrease LPS-induced IL-1 beta mRNA accumulation. Elevated intracellular cAMP does not affect IL-1 beta mRNA stability, but inhibits LPS-induced transcription initiation of IL-1 beta in U-373 MG cells. Elevated intracellular cAMP may be a negative feedback regulatory mechanism to inhibit IL-1 beta production employed by astrocytes that (unlike monocytic cells) lack a glycosyl-phosphatidylinositol (GPI)-anchored form of the LPS receptor, CD14. Whether cAMP inhibits an LPS-inducible signaling pathway or negatively affects cAMP-dependent transcription factors remains to be determined.
Willis
S A
SA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Nisen
P D
PD
D001253:Astrocytes / Q000187:drug effects / Q000276:immunology*; D015152:Blotting, Northern; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000242:Cyclic AMP