Differential activation of NF-kappa B, AP-1, and C/EBP in endotoxin-tolerant rats: mechanisms for in vivo regulation of glomerular RANTES/CCL5 expression.
Chemokines play a pivotal role in the regulation of inflammatory cell infiltration in glomerular immune injury. To characterize mechanisms relevant for the regulation of chemokine expression in vivo, the LPS-mediated model of renal inflammation in rats was used in which we have previously demonstrated that the chemokine RANTES/CCL5 is expressed and secreted in glomeruli. Glomerular RANTES/CCL5 expression in this model correlated with an increased glomerular binding activity of the transcription factors AP-1, C/EBP, and NF-kappaB. To gain further insight into the functional roles of these transcription factors in the regulation of glomerular RANTES/CCL5 expression, we cloned the rat RANTES/CCL5 promoter and established the model of in vivo LPS tolerance. In tolerant rats, LPS-induced glomerular RANTES/CCL5 expression and activation of the transcription factors AP-1 and C/EBP were significantly reduced using both consensus and rat RANTES/CCL5-specific oligonucleotides. Reduced glomerular NF-kappaB binding activity after LPS injection could be demonstrated in tolerant rats only when using rat RANTES/CCL5-specific oligonucleotides. Reduced binding activity to this RANTES/CCL5-specific NF-kappaB binding site in the context of broad NF-kappaB activation might be due to changes in transcription factor interactions or chromatin remodeling processes.
Pocock
Johanna
J
Department of Internal Medicine, Division of Nephrology and Osteology, University of Hamburg, Hamburg, Germany.
Gómez-Guerrero
Carmen
C
Harendza
Sigrid
S
Ayoub
Murwan
M
Hernández-Vargas
Purificación
P
Zahner
Gunther
G
Stahl
Rolf A K
RA
Thaiss
Friedrich
F
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D001667:Binding, Competitive / Q000235:genetics / Q000276:immunology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004731:Endotoxins / Q000008:administration & dosage / Q000276:immunology*; D006651:Histocytochemistry; D007108:Immune Tolerance / Q000235:genetics; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000276:immunology
D022762:CCAAT-Enhancer-Binding Proteins; D018946:Chemokine CCL5; D004731:Endotoxins; D016328:NF-kappa B; D018808:Transcription Factor AP-1