Oxidative stress is implicated in the pathogenesis of allergic asthma and remains an attractive target for the prevention of the disease. Herein, we investigated the anti-inflammatory effects of apocynin, a NADPH oxidase (NOX) inhibitor, in both in vitro and in vivo allergen-induced experimental asthma mediated by Th2 hyperresponsiveness. Apocynin showed potential antioxidant activities and inhibitory effects on the activation of redox-sensitive transcription factors, such as NF-jB and AP-1, induced by pro-inflammatory stimuli, such as TNF-a, lipopolysaccharide and Poly I:C, and that inhibited the production of pro-inflammatory cytokines, such as TNF-a, IL-1b and IL-6. In in vivo experimental asthma model, moreover, apocynin significantly attenuated ovalbumin-induced airway hyperresponsiveness and inflammation, as shown by the attenuation of total inflammatory cell and soluble product influx into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-4, IL-5, IL-12, IL-13 and TNF-a. Apocynin also significantly reduced lung inflammation in the tissues. Altogether, these results suggest that apocynin may be useful in the treatment of inflammatory diseases induced by oxidative stress through NOX activity. Keywords: apocynin; NADPH oxidase; oxidative stress; asthma; inflammation; NF-kB Asthma is a chronic inflammatory lung disease characterized by infiltration of inflammatory cells, including eosinophils, and airway hyperresponsiveness (AHR). 1-5 T-helper type 2 (Th2) cells, together with other inflammatory cells such as macrophages, eosinophils, mast cells and B cells, have critical roles in the initiation, development and chronicity of this disease. 1 Upon challenge with various allergens, these inflammatory cells infiltrate into the airway and contribute to the production of Th2 cytokines, such as IL-4, IL-5 and IL-13, which are found at elevated levels in asthmatic lungs. 1-5 Th2 cytokines are pivotal for B cell maturation, IgR synthesis, airway eosinophilia, mucus secretion and ultimately AHR. Specifically, IL-4 regulates allergic inflammation by promoting Th2 cell differentiation, controlling the production of IgE in B cells, stimulating B cell proliferation, inducing the upregulation of MHC class II molecules and increasing the expression of an inducible form of the low-affinity receptor for IgE (FcRII or CD23) on B lymphocytes and macrophages. 4,5 IL-5 influences the production, maturation and activation of eosinophils. 4,5 IL-13 is a potent modulator of human monocyte and B cell function. 5 IL-13 is also capable of inducing the expression of CD23 on purified human B cells and acts as a switch factor directing IgE synthesis. 5 Increased reactive oxygen species (ROS) generation, which results in imbalance between oxidative forces and the antioxidant defense systems, has been implicated in the pathogenesis of asthma. 6-8 ROS are capable of eliciting a variety of pathological changes, including the peroxidation of lipids, proteins and DNA, and the generation of chemo-attractants, enhancement of AHR,...
Pneumonia is an inflammatory disease of the lung, responsible for high morbidity and mortality worldwide. It is caused by bacteria, viruses, fungi, or other microorganisms. Streptococcus pneumoniae, a gram-positive bacterium with over 90 serotypes, is the most common causative agent. Moreover, comorbid factors including heart failure, renal disease, and pulmonary disease could increase the risk of pneumococcal pneumonia. Since the advent of the pneumococcal vaccine in the 1980s, the incidence of pneumonia has decreased significantly. However, current vaccines confer only limited protection against serotypes included in the vaccine. Thus, to overcome this limitation, new types of pneumococcal vaccines have been sought and under clinical trials. In this review, we discuss pneumonia and summarize the various types of pneumococcal vaccines in progress.
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