Redox-dependent Control: Many of the kinases, transcription factors, and subsequent gene products induced by the TLR4 ligand, LPS, can be postranslationally modified by ROS.

TLR4 Regulation: Antoehr factor that could control TLR4 function is MD2, a molecule that assocaites with the extracellular portion of TLR4 and is required for maximal TLR4 function.

Negative Regulators of TLR signalling

IkBNS: is a TLR inducible nuclear IkB protein which negatively regulates induction of a subset of TLR dependent genes through inhibition of NF-kB activity. It may be recruited to gene promoters through association with p50 and contribute to termination of NF-kB activity.

Chromatin Remodeling and Histone Acetylation: is also important in TLRsignalling. For example,  determines whether some genes are turned on versus inactive in . Since 1/2 genes in LPS tolerance are inactive whereas the other 1/2 are active, this is not a signal mechanism. Rather, the inhibition occurs at the level of gene promoters due to chromatin remodeling and histone acytylation.