Thermosensory Transient Receptor Potential Ion Channels and Asthma.

Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels.

The Degradation of Airway Epithelial Tight Junctions in Asthma Under High Airway Pressure Is Probably Mediated by Piezo-1.

Full functioning of the airway physical barrier depends on cellular integrity, which is coordinated by a series of tight junction (TJ) proteins. Due to airway spasm, edema, and mucus obstruction, positive end-expiratory alveolar pressure (also termed auto-PEEP) is a common pathophysiological phenomenon, especially in acute asthma attack. However, the influence of auto-PEEP on small airway epithelial TJs is currently unclear.

Effect of and Polymorphisms on COPD Predisposition and Lung Function in COPD Patients.

Certain transient receptor potential (TRP) channels including and are widely expressed in the respiratory tract and have been shown to be the receptors of cigarette smoke and particulate matter-the main causative factors of chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effect of and polymorphisms on COPD predisposition and lung function in COPD patients. The study enrolled 143 COPD patients and 104 smokers with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 70%.

The Cosmc-mediated effects of neutrophil elastase on T antigen expression in BEAS-2B cells.

Mucin 5AC (MUC5AC) is a highly O-glycosylated mucin secreted by human bronchial epithelial cells during pulmonary inflammatory diseases. T antigen, a component of the MUC5AC glycans, is the product of the O-glycosylation transferase T-synthase and its chaperone Cosmc. Since the expression of Cosmc is mediated by signaling pathways and inflammatory factors affecting mucin O-glycosylation, we analyzed the impact of neutrophil elastase (NE)-mediated Cosmc and T antigen expression in BEAS-2B cells derived from human bronchial epithelial cells.

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma.

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy.

The role of the XBP-1/AGR2 signaling pathway in the regulation of airway Mucin5ac hypersecretion under hypoxia.

Oversecretion of Mucin5ac (MUC5AC), which is primarily synthesized by goblet cells and is the major gel-forming mucin, is a hallmark of various pulmonary inflammatory diseases. Hypoxia is considered a common pathophysiologic feature in various pulmonary inflammatory diseases. It has been suggested that hypoxia-inducible factor 1α (HIF-1α) acts as a key factor in hypoxia-induced MUC5AC hypersecretion; however, the exact mechanisms that maintain the stability of HIF-1α and support oversecretion by airway epithelial cells under hypoxia are still unclear.

Vaccine Prophylaxis of Pneumococcal Infections in Children under Conditions of Severe Flood in the Amur River Basin.

Background: Pneumococcal infection being one of the dominant causes of acute respiratory diseases and exacerbation of chronic ones is a serious problem for human health and society. The flood in the Amur river basin in the summer of 2013 created a special zone and risk conditions for the formation of respiratory pathology in the Far-Eastern region of Russia. We aimed to give clinical and epidemiological assessment of the effectiveness of vaccination programs of respiratory viral and pneumococcal infections and generalization of regional experience in the organization of a set of measures aimed at their prevention in the postflood period in the Far-Eastern region.

MicroRNA-155 regulates lipopolysaccharide-induced mucin 5AC overproduction via a suppressor of cytokine signaling 1-mediated mechanism in human bronchial epithelial cells.

Chronic inflammatory lung diseases accompanied by Gram-negative bacteria infection are characterized by excessive mucin production. Lipopolysaccharide (LPS), the major endotoxin released from Gram-negative bacteria, is a potent inflammatory agonist for mucin overproduction. In this study, we sought to examine whether the toll-like receptor (TLR)-responsive microRNA miR-155 plays a role in LPS-provoked induction of mucin 5AC (MUC5AC) and the potential role of suppressor of cytokine signaling 1 (SOCS1) involved in this process.

Munc13‑4 mediates human neutrophil elastase‑induced airway mucin5AC hypersecretion by interacting with syntaxin2.

The overexpression and hypersecretion of mucus is a hallmark of chronic pulmonary inflammatory disease. Mucin5AC (MUC5AC) is a major component of airway gel‑forming mucin. Members of the Unc13 (Munc13) protein family act as important activators of granule exocytosis from various types of mammalian cells.

Cold-inducible RNA-binding protein mediates airway inflammation and mucus hypersecretion through a post-transcriptional regulatory mechanism under cold stress.

Acute or chronic cold exposure exacerbates chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein and is induced by various environmental stressors, such as hypothermia and hypoxia. In this study, we showed that CIRP gene and protein levels were significantly increased in patients with COPD and in rats with chronic airway inflammation compared with healthy subjects.

Transient receptor potential melastatin 8 gene polymorphism is associated with cold-induced airway hyperresponsiveness in bronchial asthma.

Background And Objective: Cold-induced airway hyperresponsiveness (CAH) is common in bronchial asthma (BA) patients and represents a problem for those living in cold climate. Transient receptor potential melastatin 8 (TRPM8) channel is the main cold temperature sensor in humans that could mediate cold response in asthmatics with CAH. No associations between TRPM8 gene polymorphisms and CAH have been reported.

Impact of Atmospheric Microparticles on the Development of Oxidative Stress in Healthy City/Industrial Seaport Residents.

Atmospheric microsized particles producing reactive oxygen species can pose a serious health risk for city residents. We studied the responses of organisms to microparticles in 255 healthy volunteers living in areas with different levels of microparticle air pollution. We analyzed the distribution of microparticles in snow samples by size and content.

Ezrin/Exocyst complex regulates mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells.

Background/aim: Increased mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process.

Effects of ATP release on mucin5AC secretion in airway epithelial cells by mechanical stretching.

This study is to determine the effects of ATP and Ca(2+) on mucin5AC (MUC5AC) overexpression in airway epithelial cells in mechanical ventilation. Oxygen was injected into the closed box used in this study to increase the pressure. Gravity-driven draining flow led to formation of a thin liquid film on the upper portion of cell monolayer, exposing cells to the tension forces at the air-liquid interface.

[Role of calcium-sensing receptor in hypoxia-induced airway mucous hypersecretion].

Objective: To explore the mechanism of calcium-sensing receptor (CaSR) in hypoxia-induced airway mucous hypersecretion.

Methods: Cultured human airway epithelial cells HBE16 by hypoxia incubator (94%N₂, 1%O₂, 5%CO₂, 37 °C). HBE16 were transfected with CaSR targeted small interfering RNA (CaSR-siRNA), pretreated with a specific activator of CaSR CaCl₂ and preincubated with various inhibitors [Gαq/11 protein inhibitor YM-254890, phospholipase C (PLC) inhibitor U73122, inositol 1, 4, 5-triphosphate receptors (IP 3R) inhibitor 2-APB and cell-permeable intracellular calcium chelator BAPTA-AM] before hypoxia.

Secretoneurin induces airway mucus hypersecretion by enhancing the binding of EGF to NRP1.

Aims: Secretoneurin(SN), a neuropeptide, has been considered a reliable marker of allergenic stimulation. However, the relationship between SN and the secretion of airway mucin remains unclear. In this study, we aimed to examine the in vitro relationship between SN and airway mucin over synthesis, as well as the signaling pathways involved.

Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion.

The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. MUC (mucin) 5AC is an important component of the airway mucus. The formation of MUC5AC is related to ATP and intracellular calcium in the epithelial cells.

[Main mediated molecules of airway shear stress-stimulated MUC5AC extracellular secretion].

Objective: To explore the main mediated molecules of mucin (MUC) 5AC extracellular secretion stimulated by airway shear stress (SS).

Methods: The 16 human bronchial epithelial (HBE) cells were cultured and randomized divided by Stata software into 5 groups: A. control group; B.

Annexin II mediates the neutrophil elastase-stimulated exocytosis of mucin 5ac.

The overexpression and hypersecretion of mucus is a hallmark of several chronic pulmonary inflammatory diseases, including chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis. Mucin 5ac (MUC5AC) is a major component of airway mucus. Annexin II (ANXII) has been reported to be expressed in various cells and is associated with the fusion of secretory vesicles.

[Effects of glycyrrhizin on airway mucus hypersecretion induced by interleukin-13 in rats].

Objective: To explore the effects of glycyrrhizin on airway mucus hypersecretion induced by interleukin-13 (IL-13) in rats.

Methods: A total of 50 SD rats were divided randomly into 5 groups with a random digit table: control group, IL-13 group, and different dosage (25, 50, 75 mg/kg) glycyrrhizin groups. The integral of expression intensity in positive cells of airway epithelium under mucus histochemical stain was calculated with modality-quantitative method.

The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats.

In a recent study, we demonstrated that transient receptor potential melastatin 8 (TRPM8), a calcium-permeable cation channel that is activated by cold temperatures, is localized in the bronchial epithelium and is upregulated in subjects with chronic obstructive pulmonary disease, which causes them to be more sensitive to cold air. In the present study, we found that exposure to cold temperatures induced ciliary ultrastructural anomalies and mucus accumulation on the epithelial surface. Male Sprague-Dawley rats were exposed to cold temperatures to determine the effects of cold air on ultrastructural changes in cilia and the airway epithelial surface.

Cortactin mediates elevated shear stress-induced mucin hypersecretion via actin polymerization in human airway epithelial cells.

Mucus hypersecretion is a remarkable pathophysiological manifestation in airway obstructive diseases. These diseases are usually accompanied with elevated shear stress due to bronchoconstriction. Previous studies have reported that shear stress induces mucin5AC (MUC5AC) secretion via actin polymerization in cultured nasal epithelial cells.

The degradation of airway tight junction protein under acidic conditions is probably mediated by transient receptor potential vanilloid 1 receptor.

Acidic airway microenvironment is one of the representative pathophysiological features of chronic inflammatory respiratory diseases. Epithelial barrier function is maintained by TJs (tight junctions), which act as the first physical barrier against the inhaled substances and pathogens of airway. As previous studies described, acid stress caused impaired epithelial barriers and led the hyperpermeability of epithelium.

Role of the JNK pathway on the expression of inflammatory factors in alveolar macrophages under mechanical ventilation.

The aim of this study was to investigate the regulatory role of the c-JUN N-terminal kinase (JNK) pathway on interleukin (IL)-8 and tumor necrosis factor (TNF)-α expression in alveolar macrophages (AMs) of injured lung. Lung injury was induced in the New Zealand white rabbit by applying continuous mechanical ventilation with or without inhibitor of JNK (SP600125), p38 (SB203580), or ERK (PD98059). Non-ventilated rabbits (controls) were compared with the different ventilation-days groups, and untreated rabbits ventilated for 3 days (controls) were compared with the different inhibitor groups.