The gasotransmitter carbon monoxide (CO) regulates fluid and electrolyte movements across epithelial tissues. However, its action on anion channels is incompletely understood. Here, we investigate the direct action of CO on the cystic fibrosis transmembrane conductance regulator (CFTR) by applying CO-releasing molecules (CORMs) to the intracellular side of excised inside-out membrane patches from cells

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury and higher concentrations are

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) SARS-CoV-1 (2002), MERS-CoV (2012) and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of anti-viral therapies. To address this, we developed an in-vitro infection model for two human coronaviruses; alphacoronavirus

Anti-retroviral therapy in HIV patients has lengthened life span but led to an increased risk for secondary co-morbidities, such as pulmonary complications characterized by vascular dysfunction. In the lung, PDGFRb+ mesenchymal cells known as pericytes intimately associate with endothelial cells and are key for their survival, both structurally and through the secretion of pro-survival factors. We

Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical

Recent clinical trials have shown improvements in neonatal outcomes after intratracheal administration of combination budesonide/surfactant (ITBS)in infants at risk of bronchopulmonary dysplasia. However, the effect of ITBSon lung function and alveolar structure is not known. We aimed to determine the effect of ITBSon lung function, parenchymal structure and inflammatory cytokine expression in a relevant

Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation

Bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is a chronic infantile lung disease that lacks curative therapies. Infants with BPD-associated PH are often exposed to hyperoxia and additional insults such as sepsis that contribute to disease pathogenesis. Animal models that simulate these scenarios are necessary to develop effective therapies; therefore, we investigated whether

Airway epithelial homeostasis is under constant threat due to continuous exposure to the external environment, and abnormally robust sensitivity to external stimuli is critical to the development of airway diseases, including asthma. Ku is a key non-homologous end-joining DNA repair protein with diverse cellular functions such as VDJ recombination and telomere length maintenance. Here we show a novel

A rapidly expanding new field of lung research has been produced by the emergence of culture-independent next-generation sequencing technologies. While pulmonary microbiome research lags behind the exploration of the microbiome in other organ systems, the field is maturing and has recently produced multiple exciting discoveries. In this Mini-Review, we will explore recent advances in our understanding

The severity of coronavirus disease 2019 (COVID-19) is linked to an increasing number of risk factors, including exogenous (environmental) stimuli such as air pollution, nicotine, and cigarette smoke. These three factors increase the expression of angiotensin I converting enzyme 2 (ACE2), a key receptor involved in the entry of SARS-CoV-2 -the etiological agent of COVID-19- into respiratory tract epithelial

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of the airway hyperresponsiveness, a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM

G551D is a major disease-associated gating mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP- and phosphorylation-dependent chloride channel. G551D causes severe CF disease by disrupting ATP-dependent channel opening, however, whether G551D affects phosphorylation-dependent channel activation is unclear. Here, we use macro patch recording and Ussing chamber

Mucosal surfaces are constantly exposed to a microbiome consisting of micro-organisms that heavily influence human immunity and health. In the lung these micro-organisms consist of bacteria, viruses and fungi and exist in a relatively low biomass state. Bacterial communities of the lung modulate local inflammation and correlate with changes in pulmonary physiology and clinical outcomes in patients

The molecular mechanisms underlying pulmonary arterial hypertension (PAH) in congenital ventricular septal defects (VSD) are unclear. We aimed to reveal molecular pathways and potential biomarkers by multi-omics analysis in VSD-PAH. Plasma from 160 children, including 120 VSD patients with/without PAH and 40 healthy children was studied by integrated proteomics, metabolomics, and bioinformatics analyses

Morbidity and mortality rates in acute lung injury (ALI) increase with age. Since alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.5 μg lipopolysaccharide/g body weight in young (3 months) and old (18 months) mice that were sacrificed

Background. Most of electronic cigarette (e-cigarette) users are also smoking tobacco cigarettes. Due to the relative novelty of this habit, very little is known on the impact of vaping on pulmonary health, even less on the potential interactions of dual e-cigarette and tobacco cigarette use. Methods. Therefore, we used well-established mouse models to investigate the impact of dual exposure to e-cigarette

The family of resistin-like molecules (RELMs) consists of four members in rodents (RELMα/FIZZ1/HIMF, RELMβ/FIZZ2, Resistin/FIZZ3, and RELMγ/FIZZ4) and two members in humans (Resistin and RELMβ), all of which exhibit inflammation-regulating, chemokine, and growth factor properties. The importance of these cytokines in many aspects of physiology and pathophysiology, especially in cardiothoracic diseases

Antenatal steroids (ANS) accelerate fetal lung maturation and reduce the incidence of respiratory distress syndrome. However, sex specificity, i.e., being less effective in males, and potential long-term neurodevelopmental sequelae, particularly with repeated courses, remain significant limitations. The differential sex response to ANS is likely mediated via the inhibitory effect of fetal androgens

The poorly understood tolerance towards high tidal volume (VT) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high VT with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion leading to improved lung function

Mechanisms driving adaptive developmental responses to chronic high altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and post-natal timeframe. We assessed lung growth and cardiopulmonary structure and function, and performed transcriptome analyses to identify

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

RSV is the leading cause of lower respiratory tract infections in children worldwide. While most develop a mild, self-limiting illness, some develop severe acute lower respiratory infection and persistent airway disease. Exposure to ambient particulate matter has been linked to asthma, bronchitis, and viral infection in multiple epidemiologic studies. We hypothesized that co-exposure to nanoparticles

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene. Although viral respiratory tract infections are, in general, more severe in patients with CF compared with the general population, a small number of studies indicate that SARS-CoV-2 does not cause a worse infection in CF. This is surprising since comorbidities including preexisting lung disease have been reported to be

Epidemiological studies suggest that environmental factors (e.g., air pollution) can influence the spread and infectivity of coronavirus disease 2019 (COVID-19); however, very few papers have investigated or discussed the mechanism behind the phenomenon. Given the fact that pollution will increase as social distancing rules are relaxed, we summarized the current understanding of how air pollution may

There is significant morbidity and mortality associated with smoke inhalation injury. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. The goal of our research was three-fold: 1) to develop a reproducible survival model of smoke inhalation injury in rats that closely resembled our previous

Hyperoxia (HO)-induced lung injury contributes to bronchopulmonary dysplasia (BPD) in preterm newborns. Intractable wheezing seen in BPD survivors is associated with airway remodeling (AWRM). Sphingosine kinase 1 (SPHK1)/ Sphingosine-1-phosphate (S1P) signaling promotes HO-mediated neonatal BPD; however, its role in the sequela of AWRM is not known. We noted an increased concentration of S1P in tracheal

Vitamin D (vitD) receptor (VDR) regulates the expression of several genes involved in signaling pathways affected in pulmonary hypertension (PH). VitD deficiency is highly prevalent in PH, and low levels are associated with poor prognosis. We investigated if vitD deficiency may predispose to or exacerbate PH. Male Wistar rats were fed with a standard or a vitD-free diet for five weeks. Then, rats were

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

Lung injury in mice induces mobilization of discrete subsets of epithelial progenitor cells to promote new airway and alveolar structures. However, whether similar cell types exist in human lung remains unresolved. Using flow cytometry, we identified a distinct cluster of cells expressing epithelial cell adhesion molecule (EpCAM), a cell surface marker expressed on epithelial progenitor cells, enriched

Background: Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. Methods: BALB/c mice received epicutaneous

Nicotine of unprecedented concentrations and purity is being inhaled by those using commercially available electronic nicotine delivery systems (ENDS). The consequences of this route of self-administration on the immunological response to inhaled allergens are not known. In mice, sensitization and inhalation challenge with the common environmental house dust mite (HDM) allergen is an experimental model

In 2019, the United States of America experienced the emergence of the vaping associated lung injury (VALI) epidemic. Vaping is now known to result in the development and progression of severe lung disease in young and healthy. Lack of regulation on electronic cigarettes in the US has resulted in over 2,000 patients and 68 deaths. We examine the clinical representation of VALI and the delve into the

Mesothelial cells are arranged as a monolayer on covering membranes that invest surfaces of body cavities like the pleura and peritoneum. Primary human mesothelial cell (HMC) cultures are needed for studying mesothelial cell homeostasis and developing disease models, such as wound healing or cancers. Remarkably, there is a paucity of useable HMC lines that are currently available which faithfully recapitulate

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

The carotid body (CB) plays a contributory role in the pathogenesis of various respiratory, cardiovascular, renal and metabolic diseases, through reflex changes in ventilation and sympathetic output. On the basis of available data about peripheral arterial chemoreception and Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV2), a potential involvement in the Coronavirus Disease 2019 (COVID-19)

Prevention of bronchopulmonary dysplasia (BPD) in premature-birth babies continues to be an unmet medical need. Intramuscular Vitamin A is currently employed in preterm neonates to prevent BPD but requires intramuscular (IM) injections in fragile neonates. We hypothesized that non-invasive inhaled delivery of vitamin A, targeted to lung, would be a more effective and tolerable strategy. We employed

Cold viruses have generally been considered fairly innocuous until the appearance of the severe acute respiratory coronavirus 2 (SARS-CoV-2) in 2019 which caused the coronavirus disease 2019 (COVID-19) global pandemic. Two previous viruses foreshadowed that a coronavirus could potentially have devastating consequences in 2002 (severe acute respiratory coronavirus (SARS-CoV)) and in 2012 (middle east

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

The past two decades have witnessed a resurgence in neutrophil research, inspired in part by the discovery of neutrophil extracellular traps (NETs) and their myriad roles in health and disease. Within the lung, dysregulation of neutrophils and NETosis have been linked to an array of diseases including pneumonia, cystic fibrosis, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary

A new form of severe acute respiratory syndrome (SARS) caused by SARS-CoV-2, called COVID-19, has become a global threat in 2020. The mortality rate from COVID-19 is high in hypertensive patients, making this association especially dangerous. There appears to be a consensus, despite the lack of experimental data, that angiotensin II (Ang II) is linked to the pathogenesis of COVID-19. This process may

Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility

E-cigarettes (eCig) are being considered as an alternative to quit cigarette smoking while their long-term effect on lung pathophysiology are unknown. Maternal eCig-vaping may be promoted and considered as a safer cigarette smoking-replacement during pregnancy thus needing further assessment. Using murine models of in utero vaping and allergic asthma with complementary in vitro experiments we tested

Prenatal smoke exposure is a risk factor for impaired lung development in children. Recent studies have indicated that Amphiregulin (AREG), which is a ligand of the epidermal growth factor receptor (EGFR), has a regulatory role in airway epithelial cell differentiation. In this study, we investigated the effect of prenatal smoke exposure on lung epithelial cell differentiation and linked this with

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

Many mouse models of allergic asthma exhibit eosinophil-predominant cellularity rather than the mixed granulocytic cytology in steroid-unresponsive severe disease. Therefore, we sought to implement a novel mouse model of antigen-driven, mixed-granulocytic, severe allergic asthma to determine biomarkers of the disease process and potential therapeutic targets. C57BL/6J, IL-6-/-, and IL-6R-/- mice were

Genetic predispositions and environmental exposures are regarded as the main predictors of respiratory disease development. Although the impact of dietary essential nutrient deficiencies on cardiovascular disease, obesity, and type II diabetes has been widely studied, it remains poorly explored in chronic respiratory diseases. Dietary choline and methionine deficiencies are common in the population

Caspase-3 and -7 are executioner caspases whose enzymatic activity is necessary to complete apoptotic cell death. Here, we questioned whether endothelial cell infection leads to caspase-3/7-mediated cell death. Pulmonary microvascular endothelial cells (PMVECs) were infected with Pseudomonas aeruginosa (PA103). PA103 caused cell swelling with a granular appearance, paralleled by intracellular caspase-3/7

Proper development of the respiratory bronchiole and alveolar epithelium proceeds through coordinated cross talk between the interface of epithelium and neighboring mesenchyme. Signals that facilitate and coordinate the cross talk as the bronchial forming canalicular stage transitions to construction of air-exchanging capillary-alveoli niche in the alveolar stage are poorly understood. Expressed within

Hypobaric hypoxia poses stress to sojourners traveling to high-altitude. A cascade of physiological changes occurs to cope with or adapt to hypobaric hypoxia. However, an insufficient physiological response to the hypoxic condition resulting from imbalanced vascular homeostasis pathways results in high-altitude pulmonary edema (HAPE). The present study aims to identify the implication of miRNAs associating

Obesity is associated with lung function impairment and respiratory diseases; however, the underlying pathophysiological mechanisms are still elusive, and therapeutic options are limited. This study examined the effects of prolonged excess fat intake on lung mechanics and microstructure and tested spermidine supplementation and physical activity as intervention strategies. C57BL/6N mice fed control