Lipopolysaccharide regulates constitutive and inducible transcription factor activities differentially in vivo in the rat.
The pathophysiology of septic shock is characterized by the induction of multiple proinflammatory genes and their products. Transcription factors play key roles in the transcription of these genes. Transcription factors may play important roles in the pathophysiology of septic shock. However, little information is available regarding the in vivo transcription factor activities during sepsis. We have studied the in vivo effects of LPS on the DNA binding activities of transcription factors Sp1 (promoter selective transcription factor), AP-2 (activating protein-2), AP-1 (activating protein-1), NF-kappaB (nuclear factor kappa B), and CREB (cAMP response element binding protein). We found that LPS up-regulated the DNA binding activity of inducible transcription factors AP-1, NF-kappaB, and CREB in a time-dependent manner, but down-regulated the DNA binding activity of constitutive transcription factors Sp1 and AP-2. Thus, LPS regulates the inducible and constitutive transcription factors differentially under in vivo conditions.
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Division of Pulmonary and Critical Care Medicine, Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
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D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics; D018805:Sepsis / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004247:DNA