IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acute Pseudomonas aeruginosa pneumonia
Lung epithelial cells are suggested to promote pathogen-induced pulmonary inflammation by the release of chemokines, resulting in enhanced recruitment of circulating leukocytes. Recent studies have shown that the interleukin-17C (IL-17C) regulates innate immune functions of epithelial cells in an autocrine manner. The aim of this study was to investigate the contribution of IL-17C to pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL-17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression of the ne...
Source: AJP: Lung Cellular and Molecular Physiology - November 8, 2016 Category: Respiratory Medicine Authors: Wolf, L., Sapich, S., Honecker, A., Jungnickel, C., Seiler, F., Bischoff, M., Wonnenberg, B., Herr, C., Schneider-Daum, N., Lehr, C.-M., Bals, R., Beisswenger, C. Tags: ARTICLES Source Type: research

Correction of lung inflammation in a F508del CFTR murine cystic fibrosis model by the sphingosine-1-phosphate lyase inhibitor LX2931
Progressive lung disease with early onset is the main cause of mortality and morbidity in cystic fibrosis patients. Here we report a reduction of sphingosine-1-phosphate (S1P) in the lung of unchallenged Cftrtm1EUR F508del CFTR mutant mice. This correlates with enhanced infiltration by inducible nitric oxide synthase (iNOS)-expressing granulocytes, B cells, and T cells. Furthermore, the ratio of macrophage-derived dendritic cells (MoDC) to conventional dendritic cells (cDC) is higher in mutant mouse lung, consistent with unprovoked inflammation. Oral application of a S1P lyase inhibitor (LX2931) increases S1P levels in mut...
Source: AJP: Lung Cellular and Molecular Physiology - November 8, 2016 Category: Respiratory Medicine Authors: Veltman, M., Stolarczyk, M., Radzioch, D., Wojewodka, G., De Sanctis, J. B., Dik, W. A., Dzyubachyk, O., Oravecz, T., de Kleer, I., Scholte, B. J. Tags: CALL FOR PAPERS Source Type: research

Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats via pleiotropic inhibition of RhoA signaling
Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathologica...
Source: AJP: Lung Cellular and Molecular Physiology - November 8, 2016 Category: Respiratory Medicine Authors: Wong, M. J., Kantores, C., Ivanovska, J., Jain, A., Jankov, R. P. Tags: ARTICLES Source Type: research

Of mice and men: correlations between microRNA-17~92 cluster expression and promoter methylation in severe bronchopulmonary dysplasia
We previously demonstrated that decreased miR-17~92 cluster expression was 1) present in lungs from human infants who died with bronchopulmonary dysplasia (BPD); 2) inversely correlated with DNA methyltransferase (DNMT) expression and promoter methylation; and 3) correlated with a subsequent diagnosis of BPD at 36 wk gestational age. We tested the hypothesis that plasma miR-17 levels would be lowest in infants who ultimately develop severe BPD. Secondly, we utilized our well-characterized murine model of severe BPD that combines perinatal inflammation with postnatal hyperoxia to test the hypothesis that alterations in lung...
Source: AJP: Lung Cellular and Molecular Physiology - November 8, 2016 Category: Respiratory Medicine Authors: Robbins, M. E., Dakhlallah, D., Marsh, C. B., Rogers, L. K., Tipple, T. E. Tags: RAPID REPORTS Source Type: research

14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy
Epoxyeicosatrienoic acids (EETs) are metabolic products of free arachidonic acid, which are produced through cytochrome P-450 (CYP) epoxygenases. EETs have anti-inflammatory, antiapoptotic, and antioxidative activities. However, the effect of EETs on cigarette smoke-induced lung inflammation is not clear. Autophagy is believed to be involved in the pathogenesis of chronic obstructive pulmonary disease. In addition, nuclear erythroid-related factor 2 (Nrf2), a transcription factor that regulates many antioxidant genes, is thought to regulate antioxidant defenses in several lung diseases. In addition, interaction between EET...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2016 Category: Respiratory Medicine Authors: Li, Y., Yu, G., Yuan, S., Tan, C., Xie, J., Ding, Y., Lian, P., Fu, L., Hou, Q., Xu, B., Wang, H. Tags: CALL FOR PAPERS Source Type: research

Real-time imaging of inflation-induced ATP release in the ex vivo rat lung
Extracellular ATP and other nucleotides are important autocrine/paracrine mediators that regulate diverse processes critical for lung function, including mucociliary clearance, surfactant secretion, and local blood flow. Cellular ATP release is mechanosensitive; however, the impact of physical stimuli on ATP release during breathing has never been tested in intact lungs in real time and remains elusive. In this pilot study, we investigated inflation-induced ATP release in rat lungs ex vivo by real-time luciferin-luciferase (LL) bioluminescence imaging coupled with simultaneous infrared tissue imaging to identify ATP-releas...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2016 Category: Respiratory Medicine Authors: Furuya, K., Tan, J. J., Boudreault, F., Sokabe, M., Berthiaume, Y., Grygorczyk, R. Tags: CALL FOR PAPERS Source Type: research

Activation of heat shock response augments fibroblast growth factor-1 expression in wounded lung epithelium
We previously showed that coincident exposure to heat shock (HS; 42°C for 2 h) and TNF-α synergistically induces apoptosis in mouse lung epithelium. We extended this work by analyzing HS effects on human lung epithelial responses to clinically relevant injury. Cotreatment with TNF-α and HS induced little caspase-3 and poly(ADP-ribose) polymerase cleavage in human small airway epithelial cells, A549 cells, and BEAS2B cells. Scratch wound closure rates almost doubled when A549 and BEAS2B cells and air-liquid interface cultures of human bronchial epithelial cells were heat shocked immediately after wounding. M...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2016 Category: Respiratory Medicine Authors: Scheraga, R. G., Thompson, C., Tulapurkar, M. E., Nagarsekar, A. C., Cowan, M., Potla, R., Sun, J., Cai, R., Logun, C., Shelhamer, J., Todd, N. W., Singh, I. S., Luzina, I. G., Atamas, S. P., Hasday, J. D. Tags: CALL FOR PAPERS Source Type: research

Attenuated heme oxygenase-1 responses predispose the elderly to pulmonary nontuberculous mycobacterial infections
Pulmonary infections with nontuberculous mycobacteria (P-NTM), such as by Mycobacterium avium complex (M. avium), are increasingly found in the elderly, but the underlying mechanisms are unclear. Recent studies suggest that adaptive immunity is necessary, but not sufficient, for host defense against mycobacteria. Heme oxygenase-1 (HO-1) has been recognized as a critical modulator of granuloma formation and programmed cell death in mycobacterial infections. Old mice (18–21 mo) infected with M. avium had attenuated HO-1 response with diffuse inflammation, high burden of mycobacteria, poor granuloma formation, and decre...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2016 Category: Respiratory Medicine Authors: Surolia, R., Karki, S., Wang, Z., Kulkarni, T., Li, F. J., Vohra, S., Batra, H., Nick, J. A., Duncan, S. R., Thannickal, V. J., Steyn, A. J. C., Agarwal, A., Antony, V. B. Tags: CALL FOR PAPERS Source Type: research

Searching for better animal models of BPD: a perspective
There have been many efforts to develop good animal models of bronchopulmonary dysplasia (BPD) to better understand the pathophysiology and mechanisms underlying development of BPD as well as to test potential strategies for its prevention and treatment. This Perspectives summarizes the features of common animal models of BPD and the strengths and limitations of such models. Potential optimal approaches to development of animal models are indicated, with the underlying concepts that require emphasis. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2016 Category: Respiratory Medicine Authors: Ambalavanan, N., Morty, R. E. Tags: PERSPECTIVES Source Type: research

Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR
Acrolein is a major thiol-reactive component of cigarette smoke (CS) that is thought to contribute to increased asthma incidence associated with smoking. Here, we explored the effects of acute acrolein exposure on innate airway responses to two common airborne allergens, house dust mite and Alternaria alternata, and observed that acrolein exposure of C57BL/6 mice (5 ppm, 4 h) dramatically inhibited innate airway responses to subsequent allergen challenge, demonstrated by attenuated release of the epithelial-derived cytokines IL-33, IL-25, and IL-1α. Acrolein and other anti-inflammatory thiol-reactive electrophiles, c...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Danyal, K., de Jong, W., O'Brien, E., Bauer, R. A., Heppner, D. E., Little, A. C., Hristova, M., Habibovic, A., van der Vliet, A. Tags: ARITCLES Source Type: research

Protein phosphatase 2A activation attenuates inflammation in murine models of acute lung injury
The objective of this study was to determine whether PP2A regulated this response in vivo by investigating the impact of pharmacologic activation of PP2A on chemokine production and activation of the MAPK cascade and lung injury using endotoxin- and bacterial-challenge models of ARDS in mice. N6-cyclopentyladenosine (N6-CPA) increased PP2A activity and inhibited endotoxin-induced cytokine production in a murine alveolar macrophage cell line. N6-CPA pretreatment in mice challenged with intratracheal endotoxin decreased chemokine production, reduced neutrophil infiltration, and attenuated lung injury. Following initiation of...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: McHugh, W. M., Russell, W. W., Fleszar, A. J., Rodenhouse, P. E., Rietberg, S. P., Sun, L., Shanley, T. P., Cornell, T. T. Tags: ARTICLES Source Type: research

Focal adhesion kinase (FAK) and mechanical stimulation negatively regulate the transition of airway smooth muscle tissues to a synthetic phenotype
The effects of mechanical forces and focal adhesion kinase (FAK) in regulating the inflammatory responses of airway smooth muscle (ASM) tissues to stimulation with interleukin (IL)-13 were investigated. Canine tracheal tissues were subjected to different mechanical loads in vitro, and the effects of mechanical load on eotaxin secretion and inflammatory signaling pathways in response to IL-13 were determined. Eotaxin secretion by tissues in response to IL-13 was significantly inhibited in muscles maintained at a higher (+) load compared with those at a lower (–) load as assessed by ELISA, and Akt activation was also r...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Wu, Y., Huang, Y., Gunst, S. J. Tags: ARTICLES Source Type: research

Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD
Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings, were collected from young and old individuals, susceptible and nonsusceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture. AECs were exposed to CS extract (CSE) or specific DAMPs. BALB/cByJ and DBA/2J mice were intranasally exposed to LL-37 and mitoch...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Pouwels, S. D., Hesse, L., Faiz, A., Lubbers, J., Bodha, P. K., ten Hacken, N. H. T., van Oosterhout, A. J. M., Nawijn, M. C., Heijink, I. H. Tags: ARTICLES Source Type: research

Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with high mortality. Macrophages and neutrophils are responsible for inflammatory responses in ALI and ARDS, which are characterized by excessive production of proinflammatory mediators in bronchoalveolar lavage fluid (BALF) and plasma. Aberrant activation of the JAK/STAT pathway is critical for persistent inflammation in many conditions such as infection and autoimmunity. Given the importance of the STAT3 transcription factor in activating macrophages and neutrophils and augmenting inflammation, we investigated the therapeutic potential of...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Zhao, J., Yu, H., Liu, Y., Gibson, S. A., Yan, Z., Xu, X., Gaggar, A., Li, P.-K., Li, C., Wei, S., Benveniste, E. N., Qin, H. Tags: CALL FOR PAPERS Source Type: research

Human lung fibroblasts produce proresolving peroxisome proliferator-activated receptor-{gamma} ligands in a cyclooxygenase-2-dependent manner
Human lung fibroblasts (HLFs) act as innate immune sentinel cells that amplify the inflammatory response to injurious stimuli. Here, we use targeted lipidomics to explore the hypothesis that HLFs also play an active role in the resolution of inflammation. We detected cyclooxygenase-2 (COX-2)-dependent production of both proinflammatory and proresolving prostaglandins (PGs) in conditioned culture medium from HLFs treated with a proinflammatory stimulus, IL-1β. Among the proresolving PGs in the HLF lipidome were several known ligands for peroxisome proliferator-activated receptor- (PPAR), a transcription factor whose ac...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Lacy, S. H., Woeller, C. F., Thatcher, T. H., Maddipati, K. R., Honn, K. V., Sime, P. J., Phipps, R. P. Tags: CALL FOR PAPERS Source Type: research