Inhibition of lipopolysaccharide-induced transcription factor Sp1 binding by spectrally pure diphosphoryl lipid A from Rhodobacter sphaeroides, protein kinase inhibitor H-8, and dexamethasone.
The transcription factor Sp1 plays a crucial role in the monocyte-specific expression of CD14, a binding site (or putative receptor) for lipopolysaccharide (LPS) complexes with LPS-binding protein (LBP). By using RAW 264.7 macrophages treated with spectrally pure deep-rough-chemotype hexa-acyl LPS from Escherichia coli D31m4, three inhibitors were found to block the binding activity of transcription factor Sp1, as measured by electrophoretic mobility shift assays. These inhibitors were diphosphoryl lipid A from Rhodobacter sphaeroides (10 microg/ml); the isoquinoline-sulfonamide H-8 (10 and 100 microM), which is thought to be a cGMP-dependent protein kinase inhibitor; and the anti-inflammatory agent dexamethasone (10 microM).
Jarvis
B W
BW
William S. Middleton Veterans Memorial Medical Center and Bacteriology Department, University of Wisconsin, Madison 53705, USA.
Qureshi
N
N
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000737:chemistry; D005938:Glucocorticoids / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D012242:Rhodobacter sphaeroides / Q000737:chemistry; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors*
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D016329:Sp1 Transcription Factor; C049596:diphosphoryl lipid A; C015482:protein kinase modulator; D003907:Dexamethasone; D017868:Cyclic AMP-Dependent Protein Kinases