MicroRNA-29b (miR-29b) expression has been shown to be reduced in non-small-cell lung cancer (NSCLC) tissues. Here, we have identified the oncogene cyclin-dependent protein kinase 6 (CDK6) as a direct target of miR-29b cancer. We hypothesized that vivo restoration and thus targeting genes important tumor initiation progression may represent an option for treatment. developed cationic lipoplexes (LPs)-based carrier efficiently delivered both vitro vivo. LPs containing (LP-miR-29b) NSCLC A549...

Cystic fibrosis (CF) is a fatal, genetic disorder that critically affects the lungs and directly caused by mutations in CF transmembrane conductance regulator (CFTR) gene, resulting defective CFTR function. Macroautophagy/autophagy highly regulated biological process provides energy during periods of stress starvation. Autophagy clears pathogens dysfunctional protein aggregates within macrophages. However, this impaired patients mice, as their macrophages exhibit limited autophagy activity....

Pulmonary infections can impair alveolar fluid clearance (AFC), contributing to formation of lung edema. Effects influenza A virus (IAV) on AFC are unknown.To determine effects IAV infection AFC, and identify intercellular signaling mechanisms underlying influenza-mediated inhibition AFC.BALB/c mice were infected intranasally with A/WSN/33 (10,000 or 2,500 focus-forming units per mouse). was measured in anesthetized, ventilated by instilling 5% bovine serum albumin into the dependent...

Cystic fibrosis is the most common inherited lethal disease in Caucasians. It caused by mutations cystic transmembrane conductance regulator (CFTR), of which cftr ΔF508 mutation common. macrophages are intrinsically defective autophagy because sequestration essential molecules within unprocessed CFTR aggregates. Defective allows Burkholderia cenocepacia (B. cepacia) to survive and replicate macrophages. Infection B. cepacia poses a great risk patients it causes accelerated lung inflammation...

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants and children worldwide. Intranasal infection BALB/c mice with RSV strain A2, but not ultraviolet-inactivated RSV, for 2 or 4 days reduced basal alveolar fluid clearance (AFC), a seminal function bronchoalveolar epithelium, caused loss AFC sensitivity to amiloride inhibition. Reduced was temporally associated increased lung water content consequence epithelial permeability cell death. also...

Cadmium is a toxic heavy metal ranked seventh on the Priority List of Hazardous Substances. As byproduct smelters, cadmium prevalent environmental contaminant. It also major component cigarette smoke, and its inhalation associated with decreased pulmonary function, lung cancer, chronic obstructive disease. Ion channels, including cystic fibrosis transmembrane conductance regulator (CFTR), play central role in maintaining fluid homeostasis functions. CFTR mostly expressed epithelial cells,...

Section:ChooseTop of pageAbstract <<MATERIALS AND METHODSRESULTSDISCUSSIONReferencesCITING ARTICLES

Both respiratory syncytial virus (RSV) and influenza A induce nucleotide/P2Y purinergic receptor-mediated impairment of alveolar fluid clearance (AFC), which contributes to formation lung edema. Although genetically dissimilar, both viruses generate double-stranded RNA replication intermediates, act as Toll-like receptor (TLR)-3 ligands. We hypothesized that RNA/TLR-3 signaling underlies nucleotide-mediated inhibition amiloride-sensitive AFC in infections. found addition the synthetic analog...

Background Patients with severe seasonal or pandemic influenza pneumonia frequently develop acute respiratory distress syndrome (ARDS). One clinical diagnostic criterion for ARDS is the PaO2:FiO2 ratio, which an index of alveolar gas exchange. However, effects H1N1 infection on ratios and related pathophysiologic readouts lung function have not been reported in mice. Methods To a method determining ratios, uninfected mice were anesthetized pentobarbital, diazepam/ketamine, inhaled...

ABSTRACT We have shown that bronchoalveolar epithelial A 1 -adenosine receptors (A -AdoR) are activated in influenza virus-infected mice. Alveolar macrophages and neutrophils also express -AdoRs, we hypothesized activation of -AdoRs on these cells will promote macrophage neutrophil chemotaxis thereby play a role the pathogenesis virus-induced acute lung injury. Wild-type (WT) C57BL/6 mice, congenic -AdoR knockout -KO) mice had undergone reciprocal bone marrow transfer were inoculated...

Alveolar type II (ATII) epithelial cells are the primary site of influenza virus replication in distal lung. Development acute respiratory distress syndrome influenza-infected mice correlates with significant alterations ATII cell function. However, impact infection on surfactant lipid metabolism has not been explored. C57BL/6 were inoculated intranasally A/WSN/33 (H1N1) (10,000 plaque-forming units/mouse) or mock-infected diluent. isolated by a standard lung digestion protocol at 2 and 6...

Oxidative stress may impair alveolar macrophage function in patients with inflammatory lung diseases or those exposed to high concentrations of oxygen. We investigated putative mechanisms injury macrophages by oxidative stress, using RAW 264.7 cells 95% oxygen for 48 h. Hyperoxia-exposed were less able phagocytose and kill Klebsiella pneumoniae than normoxic controls, despite increased production nitric oxide, a free radical important pathogen killing. Exposure hyperoxia had marked effects...

We investigated putative mechanisms by which human surfactant protein A (SP-A) effects killing of Klebsiella pneumoniae alveolar macrophages (AMs) isolated from bronchoalveolar lavagates patients with transplanted lungs. Coincubation AMs SP-A (25 μg/ml) and resulted in a 68% decrease total colony forming units 120 min compared infected the absence SP-A, this SP-A-mediated effect was abolished preincubation N G -monomethyl-l-arginine. Incubation transplant increased intracellular Ca 2+...

Rationale: Mycoplasma pneumoniae is a significant cause of pneumonia in humans.Objectives: To determine the impact mycoplasma infection and host inflammatory response on alveolar type II (ATII) cell ion transport vivo vitro.Methods: Mice were infected with M. pulmonis for measurements fluid clearance (AFC) isolation ATII cells. cells determination epithelial Na+ channel (ENaC) total surface protein levels by biotinylation Western blot vitro whole patch clamp recording measurement nitric...

Previous studies have suggested that the asthmatic responses of airway inflammation, remodeling, and hyperresponsiveness (AHR) are interrelated; in this study, we used exercise to examine nature interrelationship. Mice were sensitized challenged with ovalbumin (OVA); mice then exercised via running on a motorized treadmill at moderate intensity. Data indicate that, within lungs OVA-treated mice, attenuated production inflammatory mediators, including chemokines KC, RANTES, MCP-1...

We investigated the mechanisms by which respiratory syncytial virus (RSV) infection decreases vectorial Na+ transport across epithelial cells. Mouse tracheal (MTE) cells from either BALB/c or C57BL/6 mice and human airway H441 were grown on semipermeable supports under an air-liquid interface. Cells infected with RSV-A2 mounted in Ussing chambers for measurements of short-circuit currents (I(sc)). Infection RSV 24 hours (multiplicity = 1) resulted positive immunofluorescence antigen less...

Rationale: Previously, we demonstrated that intranasal infection of BALB/c mice with respiratory syncytial virus (RSV) resulted in an early 40% reduction alveolar fluid clearance (AFC), effect mediated via P2Y purinergic receptors.Objectives: To confirm RSV-induced inhibition AFC is by uridine triphosphate (UTP), and to demonstrate de novo pyrimidine synthesis leflunomide prevents increased UTP release after RSV infection, thereby also RSV.Methods: were infected intranasally strain A2. was...

Regulation of active Na + transport across fetal distal lung epithelial cells (FDLE) by corticosterone (CST), corticotropin-releasing hormone (CRH), and oxygen tension may be crucial for postnatal adaptation. FDLE isolated from 19-day rat fetuses (term: 22 days) were grown on permeable supports to confluent monolayers (duration 3 in 2.5, 5, 12, or 20% O 2 with 5% CO -balance N mounted Ussing chambers measurement short-circuit currents ( I sc ). had significantly higher levels total their...

Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common cause of lower tract disease in infants worldwide, treatment has progressed little past 30 years. The aim our study was to determine whether post-infection administration de novo pyrimidine synthesis inhibitors could prevent reduction alveolar fluid clearance (AFC) and hypoxemia that occurs at Day 2 after intranasal infection BALB/c mice with RSV. were infected intranasally RSV strain A2. AFC measured...

Background and purpose: Injury to the lung parenchyma is a constitutional feature shared by many diseases. The protein, phosphatase tensin homologue deleted on chromosome Ten (PTEN) major suppressor of phosphoinositide‐3 kinase/Akt signalling, vital survival pathway in parenchymal cells. Based this, we hypothesized that PTEN inhibition vivo would enhance cell tolerance stress thereby preventing acute injury. Experimental approach: We evaluated ability inhibitor, potassium bisperoxo...

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and children worldwide. We wished to determine whether intratracheal administration beta-agonists improved alveolar fluid clearance (AFC) across distal respiratory epithelium RSV-infected mice. Following intranasal infection with RSV strain A2, AFC was measured anesthetized, ventilated BALB/c mice by instillation 5% BSA into dependent lung. found that direct activation protein kinase A forskolin or...