PMID: 9442380Jan 27, 1998Paper

LPS tolerance in monocytes/macrophages: three 3' cytosins are required in the DNA binding motif for detection of upregulated NF-kappa B p50 homodimers

Immunobiology
M Frankenberger, H W Ziegler-Heitbrock

Abstract

When monocytes are stimulated with LPS (lipopolysaccharide) repeatedly then the initially high expression of the TNF (tumor necrosis factor) gene is only very low, i.e. the cells are tolerant to LPS. Tolerant cells still express the CD14 receptor and they can still be activated to mobilize NF-kappa B into nucleus. Analysis of the binding proteins employing the -605 motif of the human TNF promoter (GGGGCTGTCCC) revealed that in tolerant cells of the human monocytic cell line Mono Mac 6 there is a predominance of p50p50 of NF-kappa B. We now show that a mutant motif that exchanges the terminal 3' C for a G fails to bind the p50 homodimer that is upregulated in LPS toler ant human Mono Mac 6 cells. The same is true for nuclear extracts taken from the murine P388D1 macrophage cell line when tested with the -516 motif of the murine TNF promoter (GGGGGCTTTCCC). Here the wild type motif gives efficient binding of p50p50 that again is upregulated in tolerant cells whereas a mutant with a 3' G shows hardly any binding of p50p50. Conversely, the murine kappa light chain enhancer motif (GGGGACTTTCCG) does not efficiently bind the nuclear p50p50 from tolerant murine P388 macrophages. Binding is, however, readily detected when the 3' G is r...Continue Reading

Citations

Nov 5, 1998·The Journal of Clinical Investigation·J BohuslavR J Ulevitch
Jul 19, 2016·The Journal of Clinical Investigation·Gorjana RackovDimitrios Balomenos
Oct 3, 2001·Journal of Endotoxin Research·L Ziegler-Heitbrock
Nov 17, 2017·The Journal of Experimental Medicine·Linda QuatriniSophie Ugolini
Feb 17, 2007·The Journal of Biological Chemistry·Alla V TsytsykovaAnne E Goldfeld
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·X MaL J Montaner
Oct 9, 2018·Immunological Reviews·Linda QuatriniSophie Ugolini
Sep 17, 2005·International Journal of Immunopathology and Pharmacology·Q Liu, M R Hamblin

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