NF-kappaB Signaling in Chronic Inflammatory Airway Disease

نویسندگان

  • Michael Schuliga
  • Ivana Vancurova
چکیده

Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription. Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression). However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression. This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

P133: Targeting NF-Κb Signaling Pathway as Potential Therapeutic with Curcumin in Treatment of Multiple Sclerosis

Curcumin is active component of turmeric and isolated from the rhizome of turmeric, a phenolic natural product. One of inflammatory disease is multiple sclerosis, a multifocal chronic autoimmune inflammatory disease of the CNS, which is also known as a perivascular demyelinating disease. Studies have been shown that neuro-inflammation can have both harmful and beneficial effects on the neuronal...

متن کامل

Aldose reductase inhibition suppresses the expression of Th2 cytokines and airway inflammation in ovalbumin-induced asthma in mice.

Airway inflammation induced by reactive oxygen species-mediated activation of redox-sensitive transcription factors is the hallmark of asthma, a prevalent chronic respiratory disease. In various cellular and animal models, we have recently demonstrated that, in response to multiple stimuli, aldose reductase (AR) regulates the inflammatory signals mediated by NF-kappaB. Because NF-kappaB-mediate...

متن کامل

Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa.

We investigated the impact of inflammatory signaling in airway epithelial cells on host defense against Pseudomonas aeruginosa, a major cause of nosocomial pneumonia. In mice, airway instillation of P. aeruginosa resulted in NF-kappaB activation in the lungs that was primarily localized to the bronchial epithelium at 4 h, but was present in a variety of cell types by 24 h. We modulated NF-kappa...

متن کامل

Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling.

Inflammation is a pathologic feature of a variety of chronic kidney diseases. Several lines of evidence suggest a potential anti-inflammatory role for vitamin D in chronic kidney disease, but the underlying mechanism remains unknown. Here, the effect of the synthetic vitamin D analogue paricalcitol on renal inflammation was investigated in a mouse model of obstructive nephropathy. Paricalcitol ...

متن کامل

Intracellular signaling mechanisms underlying the expression of pro-inflammatory mediators in airway diseases.

UNLABELLED Several factors have been shown to trigger the pathogenesis of asthma and airway inflammation mechanisms. Elevated levels of pro-inflammatory cytokines including tumor necrosis factor-alpha and interleukin-1beta in the bronchoalveolar lavage fluid have been detected in asthmatic patients. Cytokines exert as potent stimuli in inflammatory responses through up-regulation of many gene e...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2015