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 mu ltiple proinflammatory genes and their products. Transcription factors play key roles in the transcription of these genes. Transcription factors may p lay important roles in the pathophysiology of septic shock. However, little information is available regarding the in vivo transcription factor activi ties during sepsis. We have studied the in vivo effects of LPS on the DNA b inding activities of transcription factors Sp1 (promoter selective transcri ption factor), AP-2 (activating protein-2), AP-1 (activating protein-1), NF -kappaB (nuclear factor kappa B), and CREB (cAMF response element binding p rotein). We found that LPS up-regulated the DNA binding activity of inducib le transcription factors AP-1, NF-kappaB, and CREB in a time-dependent mann er, but downregulated the DNA binding activity of constitutive transcriptio n factors Sp1 and AP-2. Thus, LPS regulates the inducible and constitutive transcription factors differentially under in vivo conditions. (C) 2001 Aca demic Press.