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American Journal of Respiratory Cell and Molecular Biology

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https://www.readbyqxmd.com/read/28915071/transcriptional-response-of-respiratory-epithelium-to-nontuberculous-mycobacteria
#1
Masashi Matsuyama, Andrew J Martins, Shamira Shallom, Olena Kamenyeva, Anuj Kashyap, Elizabeth P Sampaio, Juraj Kabat, Kenneth N Olivier, Adrian M Zelazny, John S Tsang, Steven M Holland
RATIONALE: The incidence of pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but host responses in respiratory epithelium infected with NTM are not fully understood. OBJECTIVE: We aimed to identify infection-relevant gene expression signatures of NTM infection of the respiratory epithelium. METHODS: We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium subsp. avium (MAC) or Mycobacterium abscessuss subsp...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28915065/targeting-hif-1%C3%AE-pdk1-axis-by-dichloroacetate-dca-suppresses-bleomycin-induced-pulmonary-fibrosis
#2
Justin Goodwin, Hyunsung Choi, Meng-Hsiung Hsieh, Michael L Neugent, Jung-Mo Ahn, Heather N Hayenga, Pankaj K Singh, David B Shackelford, In-Kyu Lee, Vladimir Shulaev, Shanta Dhar, Norihiko Takeda, Jung-Whan Kim
RATIONALE: Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences such as hypoxia contribute to their sustained activation and differentiation is poorly understood. OBJECTIVES: As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the pre-clinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28915064/the-immunopathologic-effects-of-mycoplasma-pneumoniae-and-cards-toxin-a-primate-model
#3
Diego J Maselli, Jorge L Medina, Edward G Brooks, Jacqueline J Coalson, Thirumalai R Kannan, Vicki T Winter, Molly Principe, Marianna P Cagle, Joel B Baseman, Peter H Dube, Jay I Peters
Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called Community Acquired Respiratory Distress Syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. Thirteen baboons were exposed to M. pneumoniae or CARDS toxin. At day 7 and 14, bronchoalveolar lavage fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28915063/twist1-in-hypoxia-induced-pulmonary-hypertension-through-tgf%C3%AE-smad-signaling
#4
Tadanori Mammoto, Megan Muyleart, G Ganesh Konduri, Akiko Mammoto
Pulmonary hypertension (PH) is a devastating pulmonary vascular disease characterized by aberrant muscularization of the normally non-muscularized distal pulmonary arterioles. The expression of the transcription factor, Twist1, increases in the lungs of pulmonary arterial hypertension patients. However, the mechanisms by which Twist1 controls the pathogenesis of PH remain unclear. It is becoming clear that endothelial-to-mesenchymal transition (EndMT) contributes to various vascular pathologies including PH; Twist1 is known to mediate EndMT...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28915060/long-non-coding-rna-lnrpt-is-regulated-by-pdgf-bb-and-modulates-proliferation-of-pulmonary-artery-smooth-muscle-cells
#5
Jidong Chen, Jiao Guo, Xiaolei Cui, Yan Dai, Zhixiong Tang, Junle Qu, J Usha Raj, Qinghua Hu, Deming Gou
Pulmonary artery hypertension (PAH) is a rare and fatal disorder with extensive remodeling of pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cell (PASMC). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMC, however, little is known about the role of long noncoding RNA (lncRNA) in this process. Using RNA sequencing (RNA-seq), we identified 725 lncRNAs in rat PASMC (RPASMC), 95 of which were expressed differentially in response to PDGF-BB treatment...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28886261/syndecan-2-attenuates-radiation-induced-pulmonary-fibrosis-and-inhibits-fibroblast-activation-by-regulating-pi3k-akt-rock-pathway-via-cd148
#6
Konstantin Tsoyi, Sarah G Chu, Nasly G Patino-Jaramillo, Julie Wilder, Julian Villalba, Melanie Doyle-Eisele, Jacob McDonald, Xiaoli Liu, Souheil El-Chemaly, Mark A Perrella, Ivan O Rosas
RATIONALE: Radiation-induced pulmonary fibrosis is a severe complication of patients treated with thoracic irradiation. We have previously shown that syndecan-2 reduces fibrosis by exerting alveolar epithelial cytoprotective effects. Here, we investigate whether syndecan-2 attenuates radiation-induced pulmonary fibrosis by inhibiting fibroblast activation. METHODS: C57BL/6 wild type (WT) mice and transgenic (TG) mice that overexpress human syndecan-2 in alveolar macrophages were exposed to 14 Gy whole thoracic radiation...
September 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28886250/dectin-2-is-a-c-type-lectin-receptor-that-recognizes-pneumocystis-and-participates-in-innate-immune-responses
#7
Theodore J Kottom, Deanne M Hebrink, Paige E Jenson, Paige L Marsolek, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Andrew H Limper
Pneumocystis remains an important fungal pathogen causing life-threatening pneumonia in patients with AIDS and malignancy. Lung fungal pathogens are recognized by C-type Lectin Receptors (CLRs), which bind specific ligands and stimulate innate immune responses. Previously, a role for the CLR Dectin-1 has been shown to mediate immune responses to Pneumocystis spp. For this reason, we investigated a potential role for Dectin-2. Rats with Pneumocystis pneumonia (PCP) exhibited elevated Dectin-2 mRNA levels. Soluble Dectin-2 CRD fusions protein showed binding to intact Pneumocystis carinii (Pc) and to native Pneumocystis major surface glycoprotein/glycoprotein A (Msg/gpA)...
September 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28862882/myeloid-derived-suppressor-cells-are-necessary-for-development-of-pulmonary-hypertension
#8
Andrew J Bryant, Vinayak Shenoy, Chunhua Fu, George Marek, Kyle J Lorentsen, Erica L Herzog, Mark L Brantly, Dorina Avram, Edward W Scott
RATIONALE: Pulmonary hypertension (PH) complicates the care of patients with chronic lung disease, such as idiopathic pulmonary fibrosis (IPF), resulting in a significant increase in morbidity and mortality. Disease pathogenesis is orchestrated by unidentified myeloid-derived cells. OBJECTIVE: We used murine models of PH and pulmonary fibrosis to study the role of circulating myeloid cells in disease pathogenesis and prevention. METHODS: We administered clodronate liposomes to bleomycin treated wild-type mice in order to induce pulmonary fibrosis and PH with a resulting increase in circulating bone marrow-derived cells...
September 1, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28858533/genetic-variation-in-map3k1-associates-with-ventilator-free-days-in-acute-respiratory-distress-syndrome
#9
Eric D Morrell, D Shane O'Mahony, Bradford J Glavan, Susanna Harju-Baker, Catherine Nguyen, Scott Gunderson, Aaron Abrahamson, Frank Radella Ii, Gail Rona, R Anthony Black, Mark M Wurfel
Mitogen activated protein kinase kinase kinase 1 (MAP3K1) regulates numerous intracellular signaling pathways involved in inflammation and apoptosis. We hypothesized that genetic variation in MAP3K1 might be associated with outcomes in patients with acute respiratory distress syndrome (ARDS), and that these variants would alter MAP3K1-mediated changes in inflammation and transcriptional regulation. To test this hypothesis, we genotyped single nucleotide polymorphisms (SNPs) covering linkage disequilibrium bins in MAP3K1 in 306 subjects with ARDS from the ARDSNet FACTT study, and tested for associations between MAP3K1 SNPs and ventilator-free days (VFD) and mortality...
August 31, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28853918/human-bronchial-epithelial-cell-derived-factors-from-severe-asthmatic-subjects-stimulate-eosinophil-differentiation
#10
Brittany M A Salter, Steven G Smith, Manali Mukherjee, Sophie Plante, Sakktee Krisna, Graeme Nusca, John Paul Oliveria, Anam Irshad, Gail M Gauvreau, Jamila Chakir, Parameswaran Nair, Roma Sehmi
RATIONALE: Activated bronchial epithelial cells release alarmins, including thymic stromal lymphopoietin (TSLP) that drive type 2 inflammatory responses. We hypothesize that bronchial epithelial-derived factors enhance in situ eosinophil differentiation and maturation from myeloid precursors, a process that is driven by an IL-5 rich micro-environment within asthma airways. METHODS: To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived mononuclear cells (NAMNCs) incubated with bronchial epithelial cell supernatants (BECSN) from healthy non-atopic controls (NC; n = 8), mild atopic asthmatics (MA; n = 9) and severe asthmatics (SA; n = 5)...
August 30, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28853915/rgs4-overexpression-in-lung-attenuates-airway-hyper-responsiveness-in-mice
#11
Laura A Madigan, Gordon S Wong, Elizabeth M Gordon, Wei-Sheng Chen, Nariman Balenga, Cynthia J Koziol-White, Reynold A Panettieri, Stewart J Levine, Kirk M Druey
A cardinal feature of asthma is airway hyper-responsiveness (AHR) to spasmogens, many of which activate G protein-coupled receptors (GPCRs) on airway smooth muscle (ASM) cells. Asthma subtypes associated with allergy are characterized by eosinophilic inflammation in the lung due to the type 2 immune response to allergens and proinflammatory mediators that promote AHR. The degree to which intrinsic abnormalities of ASM contribute to this phenotype remains unknown. The Regulators of G protein signaling (RGS proteins) are a large group of intracellular proteins that inhibit GPCR signaling pathways...
August 30, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28850259/tlr-7-8-ligand-s28463-suppresses-ascaris-suum-induced-allergic-asthma-in-nonhuman-primates
#12
Pierre Camateros, Cynthia Kanagaratham, Lukáš Najdekr, Dušan Holub, Jana Vrbkova, Lucie Coté, Jocelyn Fournier, Jim Gourdon, David Creery, Ron Olivenstein, Frantisek Kopriva, Tomáš Adam, David Friedecký, Petr Džubák, Marian Hajdúch, Danuta Radzioch
S28463, a ligand for Toll like receptor 7/8, has been shown to have anti-inflammatory properties in rodent models of allergic asthma. The principle goal of this study was to assess whether these anti-inflammatory effects can also be observed in a nonhuman primate (NHP) model of allergic asthma. NHPs were sensitized then challenged with natural allergen, Ascaris suum extract, then treated with S28463 orally prior to each allergen challenge. The protective effect of S28463 in NHPs was assessed by measuring various asthma related phenotypes...
August 29, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28850258/noncoding-rnas-new-players-in-pulmonary-medicine-and-sarcoidosis
#13
Oriana Salamo, Esmaeil Mortaz, Mehdi Mirsaeidi
Noncoding RNAs (ncRNAs) are coded by 98% of the human genomic DNA. They are grouped into two major classes according to their length: small ncRNAs and long ncRNAs. They regulate genome organization and stability, and physiological processes that maintain cellular homeostasis. Recently, there has emerged a large interest in ncRNAs because of their significant roles in the development of several inflammatory diseases, including sarcoidosis. Some of them were introduced as novel markers for the disease activity, such increased levels of miRNA-34a that was found in peripheral blood mononuclear cells of sarcoidosis patients reemphasizing the inflammatory component in sarcoidosis...
August 29, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28850257/cd34-differentially-regulates-contractile-and-non-contractile-elements-of-airway-reactivity
#14
Katherine Lortie, Catherine Maheux, David Gendron, Anick Langlois, Marie-Josée Beaulieu, David Marsolais, Ynuk Bossé, Marie-Renée Blanchet
RATIONALE: Airway hyperresponsiveness (AHR), a major hallmark of asthma, results from alterations of contractile and non-contractile elements of airway reactivity. CD34 is a sialomucin expressed on various cells involved in asthma, such as eosinophils and airway smooth muscle (ASM) precursors, highlighting its potential influence in AHR. OBJECTIVE: To study the role of CD34 in the regulation of contractile and non-contractile elements of AHR. METHODS: AHR was induced by chronic exposure to House Dust Mite antigen (HDM)...
August 29, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28850249/deletion-of-c-flip-from-cd11b-hi-macrophages-prevents-development-of-bleomycin-induced-lung-fibrosis
#15
Alexandra L McCubbrey, Lea Barthel, Michael P Mohning, Elizabeth F Redente, Kara J Mould, Stacey M Thomas, Sonia M Leach, Thomas Danhorn, Sophie L Gibbings, Claudia V Jakubzick, Peter M Henson, William J Janssen
Idiopathic pulmonary fibrosis is a progressive lung disease with complex pathophysiology and fatal prognosis. Macrophages (MΦ) contribute to the development of lung fibrosis, however the underlying mechanisms and specific MΦ subsets involved remain unclear. During lung injury, two subsets of lung MΦ co-exist: Siglec-Fhi resident alveolar MΦ and a mixed population of CD11bhi MΦ that primarily mature from immigrating monocytes. Using a novel inducible transgenic system driven by a fragment of the human CD68 promoter, we targeted deletion of the anti-apoptotic protein c-FLIP to CD11bhi MΦ...
August 29, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28846437/oxygen-administration-improves-survival-but-worsens-cardiopulmonary-functions-in-chlorine-exposed-rats
#16
Obiefuna C Okponyia, Matthew D McGraw, Marilyn M Dysart, Rhonda B Garlick, Jacqueline S Rioux, Angela L Murphy, Gates B Roe, Carl W White, Livia A Veress
RATIONALE: Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4h of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures exist for massive chlorine exposure, and supportive care measures lack controlled trials. METHODS: Adult rats were exposed to chlorine gas (LD58-67) in a whole-body exposure chamber, and given oxygen (0...
August 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28817310/semaphorins-and-their-roles-in-airway-biology-potential-as-therapeutic-targets
#17
Hesam Movassagh, Forough Khadem, Abdelilah S Gounni
Semaphorins are a large family of proteins originally identified as axon guidance cues which play a crucial role in neural development. They are also ubiquitously expressed beyond the nervous system and contribute to regulation of essential cell functions such as cell migration, proliferation, and adhesion. Binding of semaphorins to their receptors, including plexins and neuropilins, triggers diverse signaling pathways which are involved in the pathogenesis of various diseases from cancer to autoimmune and allergic disorders...
August 17, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28812922/a-circulating-micro-rna-signature-serves-as-a-diagnostic-and-prognostic-indicator-in-sarcoidosis
#18
Christian Ascoli, Yue Huang, Cody Schott, Benjamin A Turturice, Ahmed Metwally, David L Perkins, Patricia W Finn
Micro-RNAs (miRNAs) act as post-transcriptional regulators of gene expression. In sarcoidosis, aberrant miRNA expression may enhance immune responses mounted against an unknown antigenic agent. We tested whether a distinct miRNA signature functions as a diagnostic biomarker and explored its role as an immune modulator in sarcoidosis. Expression of miRNAs from peripheral blood mononuclear cells from subjects that met clinical and histopathologic criteria for sarcoidosis were compared to those from matched controls in the ACCESS study...
August 16, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28800254/sirt1-protects-against-systemic-sclerosis-related-pulmonary-fibrosis-by-decreasing-pro-inflammatory-and-pro-fibrotic-processes
#19
Haiyan Chu, Shuai Jiang, Qingmei Liu, Yanyun Ma, Xiaoxia Zhu, Minrui Liang, Xiangguang Shi, Weifeng Ding, Xiaodong Zhou, Hejian Zou, Feng Qian, Philip W Shaul, Li Jin, Jiucun Wang
Pulmonary fibrosis is the leading cause of death in systemic sclerosis (SSc). Sirtuin1 (SIRT1) is a deacetylase with known anti-inflammatory and anti-fibrotic activity in the liver, kidney and skin. The role of SIRT1 in SSc-related pulmonary fibrosis is unknown. In the present work, we determined that the expression of SIRT1 in peripheral blood mononuclear cells of SSc patients with pulmonary fibrosis is lower than that in SSc patients without pulmonary fibrosis. In in vivo studies of Bleomycin-induced lung fibrosis in mice, SIRT1 activation with Resveratrol reduced collagen production when it was administered either prophylactically during the inflammatory stage or after the development of fibrosis...
August 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28800253/targeting-pulmonary-endothelial-hemoglobin-%C3%AE-improves-nitric-oxide-signaling-and-reverses-pulmonary-artery-endothelial-dysfunction
#20
Roger A Alvarez, Megan P Miller, Scott A Hahn, Joseph C Galley, Eileen Bauer, Timothy Bachman, Jian Hu, John Sembrat, Dmitry Goncharov, Ana L Mora, Mauricio Rojas, Elena Goncharova, Adam C Straub
RATIONALE: Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells express hemoglobin α to control nitric oxide diffusion, but the role of this system in the pulmonary circulation has not been evaluated. OBJECTIVES: We hypothesize that up-regulation of hemoglobin α in pulmonary endothelial cells contributes to nitric oxide depletion and pulmonary vascular dysfunction in pulmonary hypertension...
August 11, 2017: American Journal of Respiratory Cell and Molecular Biology
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