An antioxidant modulates expression of receptor activator of NF-κB in asthma

Abstract

Oxidative stress plays critical roles in airway inflammation that is usually accompanied by increased vascular permeability and plasma exudation. VEGF increases vascular permeability and leads to airway inflammation. In addition, VEGF has been shown to enhance receptor activator of NF-κB (RANK) expression in endothelial cells. An aim of the study was to determine the potential role of antioxidant in the regulation of RANK expression in murine model of asthma. We have used a C57BL/6 mouse model of allergic asthma to evaluate the effect of L-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, which acts as an antioxidant, and VEGF receptor inhibitor on RANK mRNA expression. The mice develop the following pathophysiological features of asthma in the lungs: increased expression of RANK mRNA, increased number of inflammatory cells of the airways, increased vascular permeability, and increased levels of VEGF. Administration of OTC and VEGF receptor inhibitor markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that the increased RANK mRNA expression at 72 h after ovalbumin inhalation were reduced by the administration of OTC or VEGF receptor inhibitor. The results indicate that OTC and VEGF receptor inhibitor which inhibit up-regulation of VEGF expression modulate RANK expression that may be in association with the regulation of vascular permeability, and suggest that VEGF may regulate the RANK expression. These findings provide a crucial molecular mechanism for the potential use of antioxidants to prevent and/or treat asthma and other airway inflammatory disorders.

Fullerene Nanomaterials Inhibit the Allergic Response

“…We demonstrated ROS generation in human PBB that had released significantly more mediators when challenged with diesel exhaust particles compared with nonchallenged cells (35). Some evidence indicates that allergic and inflammatory skin diseases like atopic dermatitis, urticaria and psoriasis are mediated by MC-initiated oxidative stress (36) while recent studies suggest antioxidants can reduce asthma symptoms in mice (37,38). Previous studies have demonstrated that ROS, possibly from MC, play a significant role in the pathogenesis of a number of disorders such as inflammation, rheumatoid arthritis, asthma, psoriasis, urticaria, and contact dermatitis (39).…”

Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

“…Several groups found decreased mitochondrial dysfunction and oxidative stress in asthmatic mice treated with antioxidants [95-105]. For example, using a C57BL/6 mouse model of allergic asthma, Lee et al .…”

“…For example, using a C57BL/6 mouse model of allergic asthma, Lee et al . [95] studied the role of antioxidants in regulating the receptor activator of NF-kappaB expression. They evaluated the effects of the vascular growth factor receptor inhibitor and L-2-oxothiazolidine-4-carboxylic acid (a prodrug of cysteine), on the receptor activator of NF-kappaB mRNA expression.…”

Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo

“…Increased ROS generation, which results in an imbalance between oxidative forces and the antioxidant defense systems, has been implicated in the pathogenesis of asthma (Rahman et al, 1999;Dworski et al, 2000;Rahman et al, 2000;Lee et al, 2006Lee et al, , 2007Kirkham et al, 2006). ROS are capable of eliciting a variety of pathological changes, including the peroxidation of lipids, proteins, and DNA and the generation of chemoattractants, as well as enhancements of AHR, airway secretion, and vascular permeability in asthmatic airways (Barnes et al, 1990;Henricks et al, 2001;Andreadis et al, 2003).…”