Oxidative stress and redox regulation of lung inflammation in COPD
Irfan Rahman,Ian M. Adcock +1 more
TLDR
Oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation, and various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are discussed.Abstract:
Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kappaB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kappaB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kappaB-alpha kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-kappaB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression. Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kappaB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.read more
Citations
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Inflammatory responses and inflammation-associated diseases in organs
Linlin Chen,Huidan Deng,Hengmin Cui,Jing Fang,Zhicai Zuo,Junliang Deng,Yinglun Li,Xun Wang,Ling Zhao +8 more
TL;DR: Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds, potentially leading to tissue damage or disease.
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Systemic manifestations and comorbidities of COPD
TL;DR: Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities, however, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future.
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Glucocorticoid resistance in inflammatory diseases
Peter J. Barnes,Ian M. Adcock +1 more
TL;DR: Several molecular mechanisms of glucocorticoid resistance have now been identified, including activation of mitogen-activated protein (MAP) kinase pathways by certain cytokines, excessive activation of the transcription factor activator protein 1, reduced histone deacetylase-2 (HDAC2) expression, and increased P-glycoprotein-mediated drug efflux.
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Chronic obstructive pulmonary disease
TL;DR: The main cause is smoking tobacco, but other factors have been identified as mentioned in this paper, such as genetic determinants, lung growth, and environmental stimuli, which is further aggravated by exacerbations, particularly in patients with severe disease.
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New insights into the immunology of chronic obstructive pulmonary disease
TL;DR: The role of autoimmunity (autoantibodies), remodelling, extracellular matrix-derived fragments, impaired innate lung defences, oxidative stress, hypoxia, and dysregulation of microRNAs in the persistence of the pulmonary inflammation despite smoking cessation are discussed.
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