Research on NFKB

 

(1) Inhibition of Nuclear Factor Kappa B (NFkB):  An Emerging Theme in Anti-Inflammatory Therapies.
Fulvio D'Acquisto, PhD, Michael J. May, PhD and Sankar Ghosh, PhD.  Section of Immunobiology and Department of Molecular Biophysics and Biochemistry Howard Hughes Medical Institute Yale University School of Medicine New Haven, CT 06510.  Molecular Interventions 2:22-35 (2002)  

The application of anti-inflammatory therapies began thousands of years ago with the use of readily available natural resources. It is only recently, however, that the cellular and molecular mechanisms of inflammation have been appreciated sufficiently to design anti-inflammatory strategies with limited side effects. For example, salicylates and glucocorticoids, two widely used anti-inflammatory drug classes, are now known to inhibit the activation of NF-_kB, a transcription factor that regulates the inducible expression of a wide range of proinflammatory mediators. New generations of NF-_kB–targeting anti-inflammatory agents that are specific, efficacious, and cost-effective may therefore complement or replace current therapies. In this review, we describe various classes of NF- B inhibitors and discuss important unresolved issues regarding their use.

 

(2) Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50.
Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X, Yao X, Ma D, Slungaard A, Hebbel RP, Key NS, Geng JG.  J Immunol. 2004 Sep 15;173(6):4207-17.

NF-kappaB is a central transcriptional factor and a pleiotropic regulator of many genes involved in immunological responses. During the screening of a plant extract library of traditional Chinese herbal medicines, we found that NF-kappaB activity was potently inhibited by andrographolide (Andro), an abundant component of the plant Andrographis that has been commonly used as a folk remedy for alleviation of inflammatory disorders in Asia for millennia. Mechanistically, it formed a covalent adduct with reduced cysteine (62) of p50, thus blocking the binding of NF-kappaB oligonucleotide to nuclear proteins. Andro suppressed the activation of NF-kappaB in stimulated endothelial cells, which reduced the expression of cell adhesion molecule E-selectin and prevented E-selectin-mediated leukocyte adhesion under flow. It also abrogated the cytokine- and endotoxin-induced peritoneal deposition of neutrophils, attenuated septic shock, and prevented allergic lung inflammation in vivo. Notably, it had no suppressive effect on IkappaBalpha degradation, p50 and p65 nuclear translocation, or cell growth rates. Our results thus reveal a unique pharmacological mechanism of Andro's protective anti-inflammatory actions.

 

(3) Nuclear factor-kappaB: the enemy within.  Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, Unit 143, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Cancer Cell. 2004 Sep;6(3):203-8.

Numerous lines of investigation suggest that nuclear factor NF-kappaB, a proinflammatory transcription factor, could promote tumorigenesis. Various inflammatory agents, carcinogens, tumor promoters, and the tumor microenvironment activate NF-kappaB. NF-kappaB proteins themselves and proteins regulated by it have been linked to cellular transformation, proliferation, apoptosis suppression, invasion, angiogenesis, and metastasis. Constitutively activated NF-kappaB is common in wide variety of tumors. Furthermore, there exists genetic evidence that NF-kappaB mediates tumorigenesis. Thus, suppression of NF-kappaB activation should be effective in the prevention and treatment of cancer.

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