Inflammation

NF-kappa B
A technology that can reduce inflammation, and inhibit NF-kappa B from increasing inflammatory mediators would have tremendous advantages in the therapeutic arena, especially in the treatement of infected wounds.
Recent reports show that deactivating a protein called I-Kappa-B kinase beta (IKK-beta) inside the cell stops cancer progression in its tracks along with inflammation. IKK-Beta normally plays a role in healing. During an injury or infection immune system molecules, including oxygen radicals, which deplete glutathione, activate IKK-beta. Once stimulated, this protein keeps cells alive and growing. IKK-beta also promotes inflammation in damaged tissues. IKK-beta is also known to be elevated in bronchial epithelial cells and many other diseases, infected wounds, including cancer. IKK-beta also assists tumor growth in different types of cells by subverting the programmed cell death that would otherwise prevent tumor formation, thus IKK-beta promotes tumor development and growth through inflammation. IKK-beta works by activating the transcription factor nuclear factor-kappa B (NF-kappa B). NF-kappa B resides in the cytoplasm as an inactive dimer, consisting of two subunits, bound to an inhibitory protein. The inhibitory protein is degraded in response to various environmental stimuli, such as pro-inflammatory cytokines, viruses, and oxygen radicals. This allows NF-kappa B to translocate to the nucleus where it activates genes that play a role in the regulation of inflammatory responses, including genes that encode pro-inflammatory cytokines IL-2, TNF, IL-6, IL-11, IL-17. NF-kappa B also regulates NO synthetase, and genes that inhibit apoptosis, which plays a major role in tumor growth and survival. NF-kappa B when activated stops programmed cellular death, activates other inflammatory mediators, and increases Nitric Oxide synthesis and production. In patients with inflammatory diseases including infections, lung diseases like cystic fibrosis, COPD, ILD, and cancer, NF-kappa B activation is exaggerated as are other inflammatory components. Hydrogen peroxide and other oxygen radicals, such as nitrogen dioxide and peroxynitrite also activates NF-kappa B as does cellular glutathione depletion. Oxygen radicals also damage p53, a protein central to the inhibition of tumor growth. Its function is to ensure that every time a cell divides, each of the two daughter cells gets an undamaged copy of the original set of genes, free of mutations. If the cell contains damaged DNA, the p53 protein stops cellular division. Only when repairs are complete will p53 permit DNA replication to begin. But if the damage is too extensive to repair, p53 blocks the cell from dividing and commands the cell to die. The p53 protein triggers the process of programmed cell death. In at least 50 to 80 percent of all cancers, p53 is damaged and apparently useless. Thus any molecule that deactivates either IKK- beta or NF-kappa B would inhibit inflammation that could also lead to tumor development and survival. Antioxidants have been shown to inhibit NF-kappa B thus inhibit inflammation and to protect DNA and proteins like p53 from oxidative damage thus facilitate the healing process. Antioxidants like vitamin C, vitamin A, acetylcysteine, vitamin E, glutathione, and pyruvate down regulate and inhibit NF-kappa B. High levels of Nitric Oxide also inhibit NF-kappa B. Thus a technology that can reduce inflammation, and inhibit NF-kappa B from increasing inflammatory mediators would have tremendous advantages in the therapeutic arena, especially in the treatement of infected wounds.

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