Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

Abstract

Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways. These have also recently been associated with mechanisms of oxidative biology. This is of important clinical significance as the observed inefficacy of current available treatments for severe asthma is widely attributed to oxidative stress. Therefore, targeting oxidizing molecules in conjunction with inflammatory mediators and transcription factors may present a novel therapeutic strategy for asthma. In this review, we summarize TLRs and NF-кB pathways in the context of exacerbation of asthma pathogenesis and oxidative biology, and we discuss the potential use of polyphenolic flavonoid compounds, known to target these pathways and possess antioxidant activity, as potential therapeutic agents for asthma.

Cough-provocation tests with hypertonic aerosols

“…Therefore, the ability of CPTHAs to clearly differentiate asthmatic and healthy subjects is a special feature among cough-provocation tests. The asthmatic airway inflammation involves eosinophils, mast cells and lymphocytes [77]. It is possible that some of these cells might be able to sense hyperosmolarity and to secrete substances that activate jugular ganglion sensory fibres.…”

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

“…Finally, viral infection can result in enhanced production of reactive oxygen species (ROS), oxidative stress and mitochondrial dysfunction in the airway epithelium (Kim et al, 2018;Mishra et al, 2018;Wang et al, 2018). The airway epithelium of patients with chronic airway inflammatory diseases are usually under a state of constant oxidative stress which sustains the inflammation in the airway (Barnes, 2017;van der Vliet et al, 2018).…”

Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

“…Each full scan was followed by 26 MS/MS fragmentation scans using variable isolation windows with 30,000 resolution at 200 m/z, automatic gain control target 3e6, and a maximum injection time of 50 ms. The 26 variable isolation windows had the following consecutive m/z: 33,26,22,20,20,18,20,19,19,19,19,20,21,21,23,23,24,26,31,32,37,40,53,66,99, and 574.…”