Dear Jonathan,

as you know the prototypic NF-kB complex consist of a p50 and a p65 subunit and this complex can turn on gene expression via the transactivation domain on p65. This typically happens after stimulation with TLR ligands within hours. When cells are exposed to a TLR-ligand for longer periods of time (days), then there is a preferential up-regulation of p50 (triggered via the NF-kB site in its promotor). This predominant p50 forms homodimers and these can bind to the palindromic NF-kB motifs but without a transactivation domain they cannot activate gene expression. Rather they block access of p50p65 and thereby prevent transactivation. This applies to p50 and also p52.

References are:

Tolerance to Lipopolysaccharide involves mobilization of NK-kB with predominance of p50 homodimers, J Biol Chemistry 269:17001-17004, 1994, and

Role of p52 (NF-kB2) in LPS Tolerance in a Human B Cell Line, Biological Chemistry, 380: 1193-1199, 1999.

Hope that this helps.

Loems

Hi Jonathan,

A number of monocyte/macrophage tolerized genes are documented in this review:

Endotoxin tolerance: new mechanisms, molecules and clinical significance

Biswas et al 2009, Trends in Immunology Vol.30 No.10

In addition, repression of LPS inducible genes is likely to occur in primary response genes containing a particular NF-kB motif. Moreover, p50 repression acts in concert with epigenetic complexes like NcoR, HDAC1 and HDAC3.

The reference is:

Nuclear factor-κB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome Yan et al, 2012, PNAS www.pnas.org/cgi/doi/10.1073/pnas.1119842109

Sylvia

Following up on this question, can NFkB inhibit expression of proteins that has anti-inflammatory properties like PPAR alpha and is there any mechanism known by which it can do that??