AJP: Lung Cellular and Molecular Physiology 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.17{beta}-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension
17β-Estradiol (E2) exerts protective effects on right ventricular (RV) function in pulmonary arterial hypertension (PAH). Since acute exercise-induced increases in afterload may lead to RV dysfunction in PAH, we sought to determine whether E2 allows for superior RV adaptation after an acute exercise challenge. We studied echocardiographic, hemodynamic, structural, and biochemical markers of RV function in male and female rats with sugen/hypoxia (SuHx)-induced pulmonary hypertension, as well as in ovariectomized (OVX) SuHx females, with or without concomitant E2 repletion (75 μg·kg–1·day–1)...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Lahm, T., Frump, A. L., Albrecht, M. E., Fisher, A. J., Cook, T. G., Jones, T. J., Yakubov, B., Whitson, J., Fuchs, R. K., Liu, A., Chesler, N. C., Brown, M. B. Tags: CALL FOR PAPERS Source Type: research
Personalized medicine in cystic fibrosis: genistein supplementation as a treatment option for patients with a rare S1045Y-CFTR mutation
In this study, we determined that S1045Y-CFTR exhibits twofold attenuated function compared with wild-type (WT)-CFTR. We report that serine-to-tyrosine mutation leads to increased tyrosine phosphorylation of S1045Y-CFTR, followed by recruitment and binding of E3-ubiquitin ligase c-cbl, resulting in enhanced ubiquitination and passage of S1045Y-CFTR in the endosome/lysosome degradative compartments. We demonstrate that inhibition of tyrosine phosphorylation partially rescues S1045Y-CFTR surface expression and function. Based on our findings, it could be suggested that consuming genistein (a tyrosine phosphorylation inhibito...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Arora, K., Yarlagadda, S., Zhang, W., Moon, C., Bouquet, E., Srinivasan, S., Li, C., Stokes, D. C., Naren, A. P. Tags: CALL FOR PAPERS Source Type: research
Vascular endothelial-cadherin downregulation as a feature of endothelial transdifferentiation in monocrotaline-induced pulmonary hypertension
Increased pulmonary vascular resistance in pulmonary hypertension (PH) is caused by vasoconstriction and obstruction of small pulmonary arteries by proliferating vascular cells. In analogy to cancer, subsets of proliferating cells may be derived from endothelial cells transitioning into a mesenchymal phenotype. To understand phenotypic shifts transpiring within endothelial cells in PH, we injected rats with alkaloid monocrotaline to induce PH and measured lung tissue levels of endothelial-specific protein and critical differentiation marker vascular endothelial (VE)-cadherin. VE-cadherin expression by immonoblotting declin...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Nikitopoulou, I., Orfanos, S. E., Kotanidou, A., Maltabe, V., Manitsopoulos, N., Karras, P., Kouklis, P., Armaganidis, A., Maniatis, N. A. Tags: CALL FOR PAPERS Source Type: research
Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1 signaling axis in lung endothelium
Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the ...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Harijith, A., Pendyala, S., Ebenezer, D. L., Ha, A. W., Fu, P., Wang, Y.-T., Ma, K., Toth, P. T., Berdyshev, E. V., Kanteti, P., Natarajan, V. Tags: CALL FOR PAPERS Source Type: research
Proteasome function shapes innate and adaptive immune responses
The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions, such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immuno...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Kammerl, I. E., Meiners, S. Tags: REVIEWS Source Type: research
Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells
High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Rymut, S. M., Kampman, C. M., Corey, D. A., Endres, T., Cotton, C. U., Kelley, T. J. Tags: ARTICLES Source Type: research
Biosynthesis of oxidized lipid mediators via lipoprotein-associated phospholipase A2 hydrolysis of extracellular cardiolipin induces endothelial toxicity
We (66) have previously described an NSAID-insensitive intramitochondrial biosynthetic pathway involving oxidation of the polyunsaturated mitochondrial phospholipid, cardiolipin (CL), followed by hydrolysis [by calcium-independent mitochondrial calcium-independent phospholipase A2- (iPLA2)] of oxidized CL (CLox), leading to the formation of lysoCL and oxygenated octadecadienoic metabolites. We now describe a model system utilizing oxidative lipidomics/mass spectrometry and bioassays on cultured bovine pulmonary artery endothelial cells (BPAECs) to assess the impact of CLox that we show, in vivo, can be released to the extr...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Buland, J. R., Wasserloos, K. J., Tyurin, V. A., Tyurina, Y. Y., Amoscato, A. A., Mallampalli, R. K., Chen, B. B., Zhao, J., Zhao, Y., Ofori-Acquah, S., Kagan, V. E., Pitt, B. R. Tags: ARTICLES Source Type: research
Leukotriene B4 mediates macrophage influx and pulmonary hypertension in bleomycin-induced chronic neonatal lung injury
Systemically-administered bleomycin causes inflammation, arrested lung growth, and pulmonary hypertension (PHT) in the neonatal rat, similar to human infants with severe bronchopulmonary dysplasia (BPD). Leukotrienes (LTs) are inflammatory lipid mediators produced by multiple cell types in the lung. The major LTs, LTB4 and cysteinyl LTs, are suggested to contribute to BPD, but their specific roles remain largely unexplored in experimental models. We hypothesized that LTs are increased in bleomycin-induced BPD-like injury, and that inhibition of LT production would prevent inflammatory cell influx and thereby ameliorate lun...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Ee, M. T., Kantores, C., Ivanovska, J., Wong, M. J., Jain, A., Jankov, R. P. Tags: ARTICLES Source Type: research
Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone
Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proinflammatory events caus...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Ciencewicki, J. M., Verhein, K. C., Gerrish, K., McCaw, Z. R., Li, J., Bushel, P. R., Kleeberger, S. R. Tags: ARTICLES Source Type: research
Mechanisms of BDNF regulation in asthmatic airway smooth muscle
Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca2+ regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relev...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Aravamudan, B., Thompson, M. A., Pabelick, C. M., Prakash, Y. S. Tags: ARTICLES Source Type: research
AdipoR-increased intracellular ROS promotes cPLA2 and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells
Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 ph...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Chen, H.-M., Yang, C.-M., Chang, J.-F., Wu, C.-S., Sia, K.-C., Lin, W.-N. Tags: CALL FOR PAPERS Source Type: research
Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension
In conclusion, our data suggest that depletion of BMPR2 mediated by a collection of miRs induced by IL6 and subsequent STAT3 phosphorylation as a novel mechanism participating to fibroproliferative and vascular injuries in IPF. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Chen, N.-Y., D. Collum, S., Luo, F., Weng, T., Le, T.-T., M. Hernandez, A., Philip, K., Molina, J. G., Garcia-Morales, L. J., Cao, Y., Ko, T. C., Amione-Guerra, J., Al-Jabbari, O., Bunge, R. R., Youker, K., Bruckner, B. A., Hamid, R., Davies, J., Sinha, N Tags: CALL FOR PAPERS Source Type: research
A new experimental model of acid- and endotoxin-induced acute lung injury in rats
In conclusion, intratracheal instillation of HCl followed by LPS at the dose of 30 μg/g body wt results in severe diffuse alveolar damage that continues at least 72 h. This rat model of aspiration pneumonia-induced ALI will be useful for testing long-term effects of new therapeutic strategies in ALI. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Puig, F., Herrero, R., Guillamat-Prats, R., Gomez, M. N., Tijero, J., Chimenti, L., Stelmakh, O., Blanch, L., Serrano-Mollar, A., Matthay, M. A., Artigas, A. Tags: CALL FOR PAPERS Source Type: research
Lung epithelial MyD88 drives early pulmonary clearance of Pseudomonas aeruginosa by a flagellin dependent mechanism
Pseudomonas aeruginosa is a flagellated pathogen frequently causing pneumonia in hospitalized patients and sufferers of chronic lung disease. Here we investigated the role of the common Toll-like receptor (TLR) adaptor myeloid differentiation factor (MyD)88 in myeloid vs. lung epithelial cells in clearance of P. aeruginosa from the airways. Mice deficient for MyD88 in lung epithelial cells (Sftpccre-MyD88-lox mice) or myeloid cells (LysMcre-MyD88-lox mice) and bone marrow chimeric mice deficient for TLR5 (the receptor recognizing Pseudomonas flagellin) in either parenchymal or hematopoietic cells were infected with P. aeru...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Anas, A. A., van Lieshout, M. H. P., Claushuis, T. A. M., de Vos, A. F., Florquin, S., de Boer, O. J., Hou, B., van't Veer, C., van der Poll, T. Tags: CALL FOR PAPERS Source Type: research
Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury
In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quan...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Kuethe, D. O., Filipczak, P. T., Hix, J. M., Gigliotti, A. P., Estepar, R. S. J., Washko, G. R., Baron, R. M., Fredenburgh, L. E. Tags: CALL FOR PAPERS Source Type: research
