NFKB activation, inhibition

NO [inhibits NFkB activation, inhibits LPS-induced macrophage NO production]... 

Non-specific light-dependent inactivation of TNF-a-R — blocks NFkB activation] Inhibit TGF-a-R binding TGF-a-induced cell proliferation... 

Epoxy-5,10-dihydoxy-6a-angeloyloxy-9 (3-isobutyloxy germacran-8a, 12-olide (germacranolide sesquiterpene lactone) Carpesium divaricatum (Asteraceae) l iNOS expression [per inhibiting NFkB activation]... 

A major signalling pathway involves activation of a protein kinase that phosphorylates inhibitor kB proteins (IkBs) that normally inhibit the function of the nuclear transcription factor NFkB. Phosphorylation of IkB by the serine/threonine-specific IkB kinases (IKKs) leads to NFkB de-inhibition, nuclear translocation and expression of pro-inflammatory proteins such as inducible cyclooxygenase (iCOX) (which generates prostaglandins), inducible nitric oxide synthase (iNOS) (which generates vasodilatory and toxic free radicalgenerating NO) and pro-inflammatory cytokines. 

Inhibition of NFkB Activation through Down-Regulating IkB Kinase... 

In the JB6 mouse epidermal cell line, the tumor promoter TPA causes cell transformation at high frequency, marked induced NFkB activation. EGCG and TF-3 inhibited TPA-induced NFkB activity in a concentration-dependent manner. These tea polyphenols blocked TPA-induced phosphorylation of IkB at Ser 32 in the same concentration range. Moreover, the NFkB sequence-specific DNA binding activity induced by TPA was also inhibited by these polyphenols. These results confirmed that inhibition of NFkB activation is also important in evaluation of the antitumor promotion effects of tea polyphenols. 

Antioxidants, such as tea polyphenols, curcumin, and, camosol, may be expected to work by increasing intracellular GSH or total 011018, scavenging free radicals, or iron chelations. Many of the compounds classified as antioxidants that have been shown to inhibit NFkB activation are phytopolyphenols that are good peroxidase inhibitors or substrates. Many are effective at concentration that may be too low to be compatible with a radical-scavenging role, and their effects might be better explained if they were acting on a more specific enzymatic process. 

Nomura, M., Ma, W.Y., Chen, N., Bode, A.M., and Dong, Z., Inhibition of 12-0-tetra- decanoylphorbol-13-acetate-induced NFkB activation by tea polyphenols, (-)-epigallocatechin-3-gallate and theaflavins. Carcinogenesis, 21 (10), 1885-1890, 2000. 

Suzuki, Y.J., Mitsumo, M., and Packer, L., Transient overexpression of catalase does not inhibit NFkB or PMA-induced NFkB activation, Biochem. Biophys. Res. Com-mun., 210, 537, 1995. 

As to the potential link of omega-3 PUFA-derived mediators to NFkB activity, Arita et al. showed, by using a NFkB luciferase activation assay, that the EPA-derived resolvin El (RvEl) was able to inhibit TNF-a induced NFkB activation (Arita et al., 2005a). This suggests that omega-3 PUFA metabolites may be able to directly regulate the expression of NFkB associated genes. 

In an other hand, NO inhibits iNOS expression. When NO provokes the p53 accumulation, this one could in return inhibit iNOS gene transcription [154], Repression is observed in DLD-1 cells (human colon carcinoma) or Calu 6 cells (human pulmonary carcinoma) which express wild type p53. High NO concentration leads to p53 nitrosylation and inhibits the repression [114]. The wild type but not the mutated or the nitrosylated protein binds the iNOS gene promoter. Moreover, exogeneous NO produced by NO donors can inhibit NFkB activity in whole cells and in acellular preparation [155-157]. Those results have been confirmed in endothelial cells in which NO produced by eNOS inhibits NFkB activity and iNOS gene transcription [158], The inhibition can be explain in parts by NFkB sub-unit p50 nitrosylation [155], but also by its cytoplasmic inhibitor protein IxBa stabilisation (IkB proteins functionally retain NF-... 

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