Inflammatory genes

Oxidative stress has received much attention as a potentially pathogenic factor. It may promote COPD by many factors such as induction of pro-inflammatory genes in many cells including epithelial and endothelial... 

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

The importance of cross-talk in GR actions is indicated by the construction of a GR dimerisation-deficient mutant mouse in which GR is unable to dimerise and therefore bind to DNA, thus separating the DNA-binding (transactivation) and inflammatory gene repression (transrepression) activities of glucocorticoids. In these animals dexamethasone was able to inhibit AP-1- and NF-kB-mediated gene transcription,... 

NF-xB activation has been linked with atherosclerosis (Andalibi etal., 1993 Liao etui., 1993). Mice that were maintained on an atherogenic diet, which resulted in ox-LDL accumulation in the liver and arteries, showed NF-xB activation in hepatic tissues. Furthermore, inflammatory gene up-regulation corresponded to the concentration of accumulated lipid peroxides as well as genetic susceptibility to fetty-streak development. 

Bai, S.K., Lee, S.J., Na, H.J. et al. 2005. Beta-carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation. Exp Mol Med. 37 323-334. 

SET7/9 modulates p53 activity in human cancer cells in vitro and in vivo [22] and also regulates NF-/vB-dependent inflammatory genes [31]. 

Marcheselh, V. L., Hong, S., Lukiw, W. J. et al. Novel docosanoids inhibit brain ischema-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J. Biol. Chem. 278,43807-43817,2003. 

Modulation of Inflammatory Gene Expression by Trichothecene Mycotoxins... 

Trichothecene-Induced Inflammatory Gene Expression and Apoptosis... 

TRICHOTHECENE-INDUCED INFLAMMATORY GENE EXPRESSION AND APOPTOSIS... 

Pathway selective ER ligands have been reported that selectively inhibit nuclear factor kB (NF-kB) mediated gene expression [71], Since NF-kB is a pivotal regulator of pro-inflammatory gene expression, ligands that selectively inhibit the NF-kB pathway could be developed for the treatment of chronic inflammatory diseases such as arthritis, atherosclerosis, sepsis, and inflammatory bowel disease... 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

Normally corticosteroids are used for COPD treatment. The corticosteroids bind to glucocorticoid receptors and enter the nucleus of the cells, where it recruits HDAC-2. HDAC-2 deacetylates the chromatin and represses gene expression of inflammatory genes. Thus, low levels of HDAC-2 is detrimental to the treatment of COPD. Antioxidants (for removal of superoxides) or iNOS inhibitor or theophylline/curcumin for PI3K inhibition are some of the options to restore the required HDAC-2 level. 

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