Mitochondria signaling pathways in allergic asthma.

Mitochondria, as the powerhouse organelle of cells, are greatly involved in regulating cell signaling pathways, including those related to the innate and acquired immune systems, cellular differentiation, growth, death, apoptosis, and autophagy as well as hypoxic stress responses in various diseases. Asthma is a chronic complicated airway disease characterized by airway hyperresponsiveness, eosinophilic inflammation, mucus hypersecretion, and remodeling of airway. The asthma mortality and morbidity rates have increased worldwide, so understanding the molecular mechanisms underlying asthma progression is necessary for new anti-asthma drug development. The lung is an oxygen-rich organ, and mitochondria, by sensing and processing O2, contribute to the generation of ROS and activation of pro-inflammatory signaling pathways. Asthma pathophysiology has been tightly associated with mitochondrial dysfunction leading to reduced ATP synthase activity, increased oxidative stress, apoptosis induction, and abnormal calcium homeostasis. Defects of the mitochondrial play an essential role in the pro-remodeling mechanisms of lung fibrosis and airway cells' apoptosis. Identification of mitochondrial therapeutic targets can help repair mitochondrial biogenesis and dysfunction and reverse related pathological changes and lung structural remodeling in asthma. Therefore, we here overviewed the relationship between mitochondrial signaling pathways and asthma pathogenic mechanisms.

Anti-inflammatory effect of herbal traditional medicine extract on molecular regulation in allergic asthma.

Asthma is an important global health problem, and the main cause of asthma is allergic reaction and immune system dysregulation. Airway inflammation causes bronchial narrowing, and goblet cell hyperplasia leads to mucus hypersecretion that leads to airflow obstruction and difficulty breathing. The Th2 cytokines can induce allergic asthma. Camellia, Adhatoda, and Glycyrrhiza are the traditional medicines that are used in some countries. In the current study, we evaluated three herbal extracts on airway inflammatory responses in asthmatic mice. The asthma model was induced in mice that were divided into 6 groups: Phosphate-buffered saline (PBS) group, ovalbumin (OVA) group, OVA-budesonide group, OVA-Glycyrrhiza group, OVA-Camellia group, and OVA-Adhatoda group. Measurements of IL-4, IL-5, IL-13, glutamate oxaloacetate transaminase (GOT), glutamic pyruvic transaminase (GPT), IgE, histamine, percentages of eosinophils in bronchoalveolar lavage fluid (BALf), gene expression of COX-2, CCL24, CCL11, eotaxin, and histopathological study of lung were done. Adhatoda significantly attenuated the IL-4, IgE, and histamine levels. Glycyrrhiza attenuated the levels of IL-5, IL-13, GTP, GOT (on day 51), mRNA expression of eotaxin, CCL24, CCL11, and COX-2, eosinophil infiltration, mucus secretion, and goblet cell hyperplasia. Camellia decreased IL-13, GTP, COX-2 mRNA expression, mucus secretion, and goblet cell hyperplasia on day 31 and 51. We evaluated effect of three plants on allergic bio-factors. Glycyrrhiza as main anti-inflammatory treatment, Adhatoda as anti-allergic, and Camellia as anti-mucus releasing treatment can be used in attacks of allergic asthma.

Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology.

Allergic diseases such as asthma and rhinitis are common health problems that affect hundreds of millions of people in the world. T helper 2 cytokines participate in the immune responses in these diseases. Vitamin E and selenium (Se) are supplementary factors which have immunomodulatory and antioxidant effects. The present study investigated the effects of vit E + Se administration on allergic symptoms in mice models of asthma and rhinitis. Mice were treated with vit E and Se, and the levels of IL-4, IL-5, IL-13, IL-25, IL-33, total IgE, and histamine were measured. Lung histopathology was also analyzed. Our results indicated that vit E could attenuate allergic rhinitis and asthma symptoms; nevertheless, treatment with Se alone was not effective in controlling allergic symptoms. We noticed reduced airway inflammation and constriction and mucus secretion in the mice, especially when vit E was used in combination with Se. Our result suggested that vit E, especially in combination with Se, could control allergic mediators and symptoms in rhinitis and asthma and reduce pulmonary inflammation and airway mucus secretion, helping to open obstructed bronchi.

Oral Administration of Acrylamide Worsens the Inflammatory Responses in the Airways of Asthmatic Mice Through Agitation of Oxidative Stress in the Lungs.

Acrylamide is a toxic chemical substance produced when starch-rich foods are fried at high temperatures. Asthma is a chronic and complicated respiratory disease, of which genetic and environmental factors are the main triggers. Orally-received components may have an effect on asthma pathophysiology. The aim of this study was to investigate the role of AA as a stimulus in asthma. BALB/c mice were allocated into four groups as follows: two OVA-sensitized asthmatic groups, including one treated with AA by gavage feeding and one non-treated (asthma group), and two healthy (non-asthmatic) groups, one treated with AA by gavage feeding and one non-treated (negative control group). Airway hyperresponsiveness, cell count, cytokine levels in BAL fluid, lung histopathology, IgE levels, and oxidative stress indices including plasma level of MDA, pulmonary antioxidant enzymes (SOD and CAT) levels, HP content, and collagen fiber accumulation in lung tissue were measured. We found that the group of mice treated with both OVA and AA (asthmatic and AA-treated mice) experienced higher levels of asthma-associated biomarkers, including higher enhanced pause (Penh value), eosinophilic inflammation, mucus hyper secretion, goblet cell hyperplasia, total and OVA-specific IgE levels, IL-4, IL-5, and IL-13 levels than the group sensitized only with OVA (asthmatic mice). The OVA-AA-treated mice also experienced worsened levels of oxidative stress indicators. Healthy (non-asthmatic) mice that only received AA were in similar conditions to healthy untreated mice (negative control group). The OVA-AA-treated group showed more severe allergic asthma symptoms in comparison to the group only sensitized with OVA. Therefore, food/water contaminated with AA can act as a stimulant of allergic asthma and exacerbate the bronchial inflammatory responses.

Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma.

INTRODUCTION AND OBJECTIVES: Allergic asthma is a complex chronic disease of the respiratory system presenting with cough, dyspnea, wheezing and airway obstruction. More than 300 million people of all age spectrums suffer from asthma worldwide. Immunological and inflammatory processes are main contributors to asthma. Cytokines produced by T helper 2 lymphocytes play main roles in asthma development and progression. Silymarin, a therapeutic agent with anti-oxidative properties, is a main component of Silybium marinum. We herein aimed to compare the anti-inflammatory and anti-allergic effects of two silymarin isomers, isosilybin A and silydianin, in the treatment of allergic asthma. MATERIALS AND METHODS: After isolating and purifying isosilybin A and silydianin, Balb/c mouse model of allergic asthma was produced using ovalbumin injection. Seventy mice were categorized into five (1 normal and 4 asthmatic) groups (n = 14 per group). Mice in three of four asthmatic groups were treated with either isosilybin A, silydianin or budesonide. The 4th asthmatic group was used as positive control, with the non-asthmatic group serving as negative control. Airway hyperresponsiveness (AHR) and levels of IL-4, IL-5 and IL-13 in the BAL fluid were determined. Gene expressions of IL-4, IL-5, IL-13 and MUC5ac, as well as IgE serum level were also measured. Cellular composition of BAL fluid and lungs histopathology were finally investigated. RESULTS: Isosilybin A and silydianin reduced eosinophilic infiltration of lungs, IL-4 and IL-5 levels in BAL fluid, IL-4 and IL-5 gene expressions, as well as AHR in Balb/c mouse model of asthma. However, no significant changes were observed in IL-13 level and mucus hyper-secretion. CONCLUSION: According to our study, isosilybin A and silydianin can control main symptoms of asthma by modulating immune responses.

Critical role of Toll-like receptors in pathophysiology of allergic asthma.

Allergic asthma is an airway disease, characterized by reversible bronchoconstriction, chronic inflammation of the airway, and thickness of smooth muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2-adaptive immune response, in which innate immunity plays a key role. Recently TLRs have received more and more attention as they are central to orchestrate the innate immune responses. TLRs are localized as integral membrane or intracellular glycoproteins with those on the cell surface sensing microbial antigens and the ones, localized in intracellular vesicles, sensing microbial nucleic acid species. Having recognized microbial antigens, TLRs conduct the immune response towards a pro- or anti-allergy response. As a double-edged sword, they could initiate either harmful or helpful responses by the immune system in case of allergic asthma. In the current review, we will describe the role of TLRs and their signaling pathways in allergic asthma.