Immediate and delayed potentiating effects of tumor necrosis factor-{alpha} on TRPV1 sensitivity of rat vagal pulmonary sensory neurons
In conclusion, a brief pretreatment with TNFα induced both immediate and delayed potentiating effects on the TRPV1 sensitivity in pulmonary sensory neurons, and the production of COX-2 arachidonic acid metabolites plays a major role in the immediate sensitizing effect of TNFα. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Hsu, C.-C., Lin, Y. S., Lin, R.-L., Lee, L.-Y. Tags: RESEARCH ARTICLE Source Type: research

Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function
Innate immune cells of the respiratory tract are the first line of defense against pathogenic and environmental insults. Failure of these cells to perform their immune functions leaves the host susceptible to infection and may contribute to impaired resolution of inflammation. While combustible tobacco cigarettes have been shown to suppress respiratory immune cell function, the effects of flavored electronic cigarette liquids (e-liquids) and individual flavoring agents on respiratory immune cell responses are unknown. We investigated the effects of seven flavored nicotine-free e-liquids on primary human alveolar macrophage...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Clapp, P. W., Pawlak, E. A., Lackey, J. T., Keating, J. E., Reeber, S. L., Glish, G. L., Jaspers, I. Tags: RESEARCH ARTICLE Source Type: research

Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and emphysema in a predictive mouse model not via CB1 receptor activation
Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity wi...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Helyes, Z., Kemeny, A., Cseko, K., Szoke, E., Elekes, K., Mester, M., Sandor, K., Perkecz, A., Kereskai, L., Mark, L., Bona, A., Benko, A., Pinter, E., Szolcsanyi, J., Ledent, C., Sperlagh, B., Molnar, T. F. Tags: RESEARCH ARTICLE Source Type: research

Reduced carboxylesterase 1 is associated with endothelial injury in methamphetamine-induced pulmonary arterial hypertension
Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH), but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. Although no difference in CYP2D6 expression was seen by lung immunofluorescence, CES1 expression was significantly reduced in endothelium of METH-PAH microvessels. Mass spectrometry analysis showed that healthy pulmonary microvascular endothelial cells (PMVECs) have the capacity to b...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Orcholski, M. E., Khurshudyan, A., Shamskhou, E. A., Yuan, K., Chen, I. Y., Kodani, S. D., Morisseau, C., Hammock, B. D., Hong, E. M., Alexandrova, L., Alastalo, T.-P., Berry, G., Zamanian, R. T., de Jesus Perez, V. A. Tags: RESEARCH ARTICLE Source Type: research

TGF-{beta}1 induces Fstl1 via the Smad3-c-Jun pathway in lung fibroblasts
Transforming growth factor (TGF)-β1 has long been regarded as a central mediator of tissue fibrosis. Follistatin-like 1 (Fstl1) is a crucial profibrotic glycoprotein that is upregulated in fibrotic lung tissues, and it promotes fibrogenesis via facilitating TGF-β signaling. Here we examined the signaling pathway by which TGF-β1 upregulates Fstl1 expression in mouse pulmonary fibroblasts. TGF-β1 regulated Fstl1 expression at both the transcriptional and translational levels. Although TGF-β1 rapidly activated the Smad, MAPK, and Akt pathways in lung fibroblasts, only Smad2/3 inhibition eliminated TGF...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Zheng, X., Qi, C., Zhang, S., Fang, Y., Ning, W. Tags: RESEARCH ARTICLE Source Type: research

Decreased phosphatase PTEN amplifies PI3K signaling and enhances proinflammatory cytokine release in COPD
In conclusion, oxidative stress reduces PTEN protein levels, which may result in increased PI3K signaling and amplification of inflammation in COPD. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Yanagisawa, S., Baker, J. R., Vuppusetty, C., Fenwick, P., Donnelly, L. E., Ito, K., Barnes, P. J. Tags: RESEARCH ARTICLE Source Type: research

Role of apoptosis and autophagy in tuberculosis
Tuberculosis (TB) is one of the oldest known human diseases and is transmitted by the bacteria Mycobacterium tuberculosis (Mtb). TB has a rich history with evidence of TB infections dating back to 5,800 b.c. TB is unique in its ability to remain latent in an individual for decades, with the possibility of later reactivation, causing widespread systemic symptoms. Currently, it is estimated that more than one-third of the world’s population (~2 billion people) are infected with Mtb. Prolonged periods of therapy and complexity of treatment regimens, especially in active infection, have led to poor compliance in patients...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Lam, A., Prabhu, R., Gross, C. M., Riesenberg, L. A., Singh, V., Aggarwal, S. Tags: REVIEW Source Type: research

Autophagy as a double-edged sword in pulmonary epithelial injury: a review and perspective
Pulmonary epithelial cells form the first line of defense of human airways against foreign irritants and also represent as the primary injury target of these pathogenic assaults. Autophagy is a revolutionary conserved ubiquitous process by which cytoplasmic materials are delivered to lysosomes for degradation when facing environmental and/or developmental changes, and emerging evidence suggests that autophagy plays pivotal but controversial roles in pulmonary epithelial injury. Here we review recent studies focusing on the roles of autophagy in regulating airway epithelial injury induced by various stimuli. Articles eligib...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Li, Z.-Y., Wu, Y.-F., Xu, X.-C., Zhou, J.-S., Wang, Y., Shen, H.-H., Chen, Z.-H. Tags: REVIEW Source Type: research

Pulmonary toxicity of e-cigarettes
Electronic cigarettes (e-cigarettes or e-cigs) are designed to heat and aerosolize mixtures of vegetable glycerin, propylene glycol, nicotine, and flavoring additives, thus delivering nicotine by inhalation in the absence of combustion. These devices were originally developed to facilitate smoking cessation and have been available in the United States for over a decade. Since 2010, e-cig use has expanded rapidly, especially among adolescents, despite a paucity of short- and long-term safety data. Patterns of use have shifted to include never smokers and many dual users of e-cigs and combustible tobacco products. Over the l...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2017 Category: Respiratory Medicine Authors: Chun, L. F., Moazed, F., Calfee, C. S., Matthay, M. A., Gotts, J. E. Tags: REVIEW Source Type: research

Therapeutic blockade of CD54 attenuates pulmonary barrier damage in T cell-induced acute lung injury
Acute respiratory distress syndrome (ARDS) is a serious, often fatal condition without available pharmacotherapy. Although the role of innate cells in ARDS has been studied extensively, emerging evidence suggests that T cells may be involved in disease etiology. Staphylococcus aureus enterotoxins are potent T-cell mitogens capable of triggering life-threatening shock. We demonstrate that 2 days after inhalation of S. aureus enterotoxin A, mice developed T cell-mediated increases in vascular permeability, as well as expression of injury markers and caspases in the lung. Pulmonary endothelial cells underwent sequential pheno...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Svedova, J., Menoret, A., Mittal, P., Ryan, J. M., Buturla, J. A., Vella, A. T. Tags: RESEARCH ARTICLE Source Type: research

TNF{alpha} decreases mitochondrial movement in human airway smooth muscle
We examined mitochondrial movement in human ASM cells and hypothesized that, at basal [Ca2+]cyt levels, mitochondrial movement is necessary to establish proximity of mitochondria to the SR and that, during the transient increase in [Ca2+]cyt induced by agonist stimulation, mitochondrial movement is reduced, thereby promoting transient mitochondrial Ca2+ uptake. We further hypothesized that airway inflammation disrupts basal mitochondrial movement via a reduction in Miro and Milton expression, thereby disrupting the ability of mitochondria to establish proximity to the SR and, thus, reducing transient mitochondrial Ca2+ upt...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Delmotte, P., Zavaletta, V. A., Thompson, M. A., Prakash, Y. S., Sieck, G. C. Tags: RESEARCH ARTICLE Source Type: research

Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells
In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Pan, S., Sharma, P., Shah, S. D., Deshpande, D. A. Tags: RESEARCH ARTICLE Source Type: research

Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia
Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFN to mod...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Wu, M., Gibbons, J. G., DeLoid, G. M., Bedugnis, A. S., Thimmulappa, R. K., Biswal, S., Kobzik, L. Tags: RESEARCH ARTICLE Source Type: research

Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity
Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa. Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Torres, I. M., Demirdjian, S., Vargas, J., Goodale, B. C., Berwin, B. Tags: RESEARCH ARTICLE Source Type: research

Does lack of glutathione peroxidase 1 gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?
Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing glutathione peroxidase 1 (GPx1) gene expression increases the injurious effects of hyperoxia (Hyp). GPx1+/+ and GPx1–/– C57Bl/6J mice were exposed to 21% O2 (Air) or 40% O2 (Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pu...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Bouch, S., OReilly, M., de Haan, J. B., Harding, R., Sozo, F. Tags: RESEARCH ARTICLE Source Type: research