COVID-19: Clean up on IL-6.
PMID: 32750259 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - August 4, 2020 Category: Respiratory Medicine Authors: Hedrick TL, Murray BP, Hagan RS, Mock JR Tags: Am J Respir Cell Mol Biol Source Type: research

Repair of the Lung by Treg Cells.
PMID: 32721214 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 28, 2020 Category: Respiratory Medicine Authors: Cipolla EM, Alcorn JF Tags: Am J Respir Cell Mol Biol Source Type: research

Inducible Epithelial Resistance Against Coronavirus Pneumonia in Mice.
ckey BF PMID: 32706609 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 24, 2020 Category: Respiratory Medicine Authors: Evans SE, Tseng CK, Scott BL, Höök AM, Dickey BF Tags: Am J Respir Cell Mol Biol Source Type: research

Increasing Sphingolipid Synthesis Alleviates Airway Hyperreactivity.
CONCLUSIONS: This study identifies the manipulation of sphingolipid synthesis as a novel metabolic therapeutic strategy to alleviate airway hyperreactivity. PMID: 32706610 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 24, 2020 Category: Respiratory Medicine Authors: Heras AF, Veerappan A, Silver RB, Emala CW, Worgall TS, Perez-Zoghbi J, Worgall S Tags: Am J Respir Cell Mol Biol Source Type: research

A Micro-Engineered Airway Lung-Chip Models Key Features of Viral-Induced Exacerbation of Asthma.
In conclusion, our micro-engineered Airway Lung-Chip provides a novel human-relevant platform for exploring the complex mechanisms underlying viral-induced asthma exacerbation. Our data suggest that IL-13 may impair the hosts' ability to mount an appropriate and coordinated immune response to rhinovirus infection. We also show that the Airway Lung-Chip can be used to assess the efficacy of modulators of the immune response. PMID: 32706623 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 24, 2020 Category: Respiratory Medicine Authors: Nawroth JC, Lucchesi C, Cheng D, Shukla A, Ngyuen J, Shroff T, Varone A, Karalis K, Lee HH, Alves S, Hamilton GA, Salmon M, Villenave R Tags: Am J Respir Cell Mol Biol Source Type: research

Cellular Source of Cysteinyl Leukotrienes following Chlorine Exposure.
Abstract Exposure of the mouse to high concentrations of chlorine leads to the synthesis of cysteinyl leukotrienes (cysLTs). CysLTs contribute to chlorine-induced airway hyperresponsiveness. The aim of the current study was to determine the cellular source of the cysLTs. To achieve this aim we exposed mice to 100 ppm of chlorine for 5 mins. Intranasal instillation of clodronate in liposomes and of diphtheria toxin in CD11c-DTR mice was used to deplete macrophages. CCR2-/- mice were used to assess the contribution of recruited macrophages. Eosinophils and neutrophils were depleted with specific antibodies. Platelet...
Source: Am J Respir Cell Mol... - July 22, 2020 Category: Respiratory Medicine Authors: McGovern T, Ano S, Farahnak S, McCuaig S, Martin JG Tags: Am J Respir Cell Mol Biol Source Type: research

Mitochondrial Fission Mediated Cigarette Smoke-induced Pulmonary Endothelial Injury.
In this study, we hypothesized that CS caused endothelial injury via imbalance of mitochondrial fusion and fission and resultant mitochondrial oxidative stress and dysfunction. We noted that CS altered mitochondrial morphology by shortening mitochondrial networks and causing perinuclear accumulation of damaged mitochondria in primary rat lung microvascular endothelial cells (LMVEC). We also found that CS increased mitochondrial fission likely by decreasing Drp1-S637 and increasing FIS1, Drp1-S616 phosphorylation, mitochondrial translocation and tetramerization and reduced mitochondrial fusion likely by decreasing Mfn2 in L...
Source: Am J Respir Cell Mol... - July 16, 2020 Category: Respiratory Medicine Authors: Wang Z, White A, Wang X, Ko J, Choudhary G, Lange T, Rounds S, Lu Q Tags: Am J Respir Cell Mol Biol Source Type: research

Advances in Alpha-1 Antitrypsin Gene Therapy.
Abstract Alpha-1 antitrypsin deficiency (AATD), characterized by low levels of circulating serine protease inhibitor alpha-1 antitrypsin (AAT), results in emphysematous destruction of the lung. Inherited serum deficiency disorders, such as hemophilia and AATD, have been considered ideal candidates for gene therapy. While viral vector-meditated transduction of the liver have demonstrated utility in hemophilia, similar success has not been achieved for AATD. The challenge for AAT gene therapy is achieving protective levels of AAT locally in the lung and mitigating potential liver toxicities linked to systemically ad...
Source: Am J Respir Cell Mol... - July 15, 2020 Category: Respiratory Medicine Authors: Lorincz R, Curiel DT Tags: Am J Respir Cell Mol Biol Source Type: research

TGF- β Promotes Metabolic Reprogramming in Lung Fibroblasts via mTORC1-dependent ATF4 Activation.
TGF-β Promotes Metabolic Reprogramming in Lung Fibroblasts via mTORC1-dependent ATF4 Activation. Am J Respir Cell Mol Biol. 2020 Jul 15;: Authors: O'Leary EM, Tian Y, Nigdelioglu R, Witt LJ, Cetin-Atalay R, Meliton AY, Woods PS, Kimmig LM, Sun KA, Gökalp GA, Mutlu GM, Hamanaka RB Abstract Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-β-dependent differentiation of lung fibroblasts into myofibroblasts, leading to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by myofibroblasts requires de...
Source: Am J Respir Cell Mol... - July 15, 2020 Category: Respiratory Medicine Authors: O'Leary EM, Tian Y, Nigdelioglu R, Witt LJ, Cetin-Atalay R, Meliton AY, Woods PS, Kimmig LM, Sun KA, Gökalp GA, Mutlu GM, Hamanaka RB Tags: Am J Respir Cell Mol Biol Source Type: research

You Say You Want a Resolution (of Fibrosis).
Abstract In pathological fibrosis, aberrant tissue remodeling with excess extracellular matrix leads to organ dysfunction and eventual morbidity. Diseases of fibrosis create significant global health and economic burdens and are often deadly. Although fibrosis has traditionally been thought of as an irreversible process, a growing body of evidence demonstrates that organ fibrosis can reverse in certain circumstances, especially if an underlying cause of injury can be removed. This body of evidence has uncovered more and more contributors to persistent and non-resolving tissue fibrosis. Here we review the present k...
Source: Am J Respir Cell Mol... - July 8, 2020 Category: Respiratory Medicine Authors: Atabai K, Yang CD, Podolsky MJ Tags: Am J Respir Cell Mol Biol Source Type: research

Poly(ADP-ribose) Polymerase Inhibition in Acute Lung Injury: A Re-emerging Concept.
Abstract Poly(ADP-ribose) polymerase 1 (PARP1), the major isoform of a family of ADP-ribosylating enzymes, has been implicated in the regulation of various biological processes including DNA repair, gene transcription and cell death. The concept that PARP1 becomes activated in acute lung injury (ALI), and pharmacological inhibition or genetic deletion of this enzyme can provide therapeutic benefits has emerged over 20 years ago. The current article provides an overview of the cellular mechanisms involved in the pathogenetic roles of PARP1 in ALI, and overviews the preclinical data supporting the efficacy of PARP i...
Source: Am J Respir Cell Mol... - July 8, 2020 Category: Respiratory Medicine Authors: Szabo C, Martins V, Liaudet L Tags: Am J Respir Cell Mol Biol Source Type: research

KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability.
Abstract KD025 is a ROCK2 inhibitor currently being tested in clinical trials for treatment of fibrotic lung diseases. The therapeutic effects of KD025 are partly due to its inhibition of profibrotic pathways and fat metabolism. However, whether KD025 affects pulmonary microvascular endothelial cell (PMVEC) function is unknown, despite evidence that alveolar capillary membrane disruption constitutes major causes of death in fibrotic lung diseases. We hypothesized that KD025 regulates PMVEC metabolism, pH, migration and survival, a series of inter-related functional characteristics that determine pulmonary barrier ...
Source: Am J Respir Cell Mol... - July 6, 2020 Category: Respiratory Medicine Authors: Lee JY, Stevens RP, Kash M, Zhou C, Koloteva A, Renema P, Paudel SS, Stevens T Tags: Am J Respir Cell Mol Biol Source Type: research

Upregulation of CD32 in T Cells from Infants with Severe Respiratory Syncytial Virus Disease: A New Costimulatory Pathway?
PMID: 32609012 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 1, 2020 Category: Respiratory Medicine Authors: Sananez I, Raiden S, Holgado MP, Seery V, De Lillo L, Davenport C, Ferrero F, Peeples ME, Geffner J, Arruvito L Tags: Am J Respir Cell Mol Biol Source Type: research

July Highlights/Papers by Junior Investigators/NIH News.
Authors: PMID: 32609013 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 1, 2020 Category: Respiratory Medicine Tags: Am J Respir Cell Mol Biol Source Type: research

Age-dependent Differences in T Cell Responses to Influenza A Virus.
Abstract Respiratory infections from influenza A virus cause substantial morbidity and mortality in children relative to adults. T cells play a critical role in the host response to influenza A virus by supporting the innate and humoral responses, mediating cytotoxic activity, and promoting recovery. There are age-dependent differences in the number, subsets, and localization of T cells, which impact the host response to pathogens. In this article, we first review how T cells recognize influenza A virus and examine differences in the resting T cell populations between juveniles and adults. Next, we describe how th...
Source: Am J Respir Cell Mol... - July 1, 2020 Category: Respiratory Medicine Authors: Prigge AD, Ma R, Coates BM, Singer BD, Ridge KM Tags: Am J Respir Cell Mol Biol Source Type: research

Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension.
CONCLUSIONS: In term lambs with MAS and PPHN, Qp and bDO2 over the first 6h are higher by targeting SpO2 in the 95-99% range. However, 90-94% target range is associated with significantly lower FiO2 and lung oxidative stress. Clinical trials comparing 90-94% vs. 95-99% SpO2 target range in term infants with PPHN are warranted. PMID: 32609558 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - July 1, 2020 Category: Respiratory Medicine Authors: Rawat M, Chandrasekharan P, Gugino SF, Koenigsknecht C, Nielsen L, Wedgwood S, Mathew B, Nair J, Steinhorn R, Lakshminrusimha S Tags: Am J Respir Cell Mol Biol Source Type: research

Airway Epithelial Telomere Dysfunction Drives Remodeling Similar to Chronic Lung Allograft Dysfunction.
CONCLUSIONS: These findings demonstrate that telomere dysfunction isolated to airway epithelial cells leads to airway-centric lung remodeling and fibrosis similar to that observed in patients with CLAD and suggest that lung epithelial cell telomere dysfunction may be a molecular driver of CLAD. PMID: 32551854 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - June 18, 2020 Category: Respiratory Medicine Authors: Naikawadi RP, Green G, Jones KD, Achtar-Zadeh N, Mieleszko JE, Arnould I, Kukreja J, Greenland J, Wolters PJ Tags: Am J Respir Cell Mol Biol Source Type: research

ATF4 Mediates Mitochondrial Unfolded Protein Response (UPRmt) in Alveolar Epithelial Cells.
In conclusion, ER stress induces ATF4-dependent UPRmt and mitochondrial dysfunction, indicating a novel mechanism by which ER stress contributes to the pathogeneses of a variety of pulmonary disorders. PMID: 32551949 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - June 18, 2020 Category: Respiratory Medicine Authors: Jiang D, Cui H, Xie N, Banerjee S, Liu R, Dai H, Thannickal VJ, Liu G Tags: Am J Respir Cell Mol Biol Source Type: research

Nasal Wash Cytokines During Respiratory Viral Infection in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients.
Abstract Allogeneic hematopoietic cell transplant (alloHCT) recipients are at increased risk of complications from viral respiratory tract infections (vRTIs). We measured cytokine concentrations in nasal washes (NWs) from pediatric alloHCT recipients to better understand their local response to vRTI. Forty-one immunologic analytes were measured in 70 NWs, collected during and after vRTI, from 15 alloHCT recipients (median age 11 years) with 19 episodes of vRTI. These were compared with NW cytokine concentrations from an independent group of otherwise healthy patients. AlloHCT recipients are able to produce a local...
Source: Am J Respir Cell Mol... - June 17, 2020 Category: Respiratory Medicine Authors: Flerlage T, Souquette A, Allen EK, Brahm T, Crawford JC, Tang L, Sun Y, Maron G, Wolf J, Triplett B, Thomas PG Tags: Am J Respir Cell Mol Biol Source Type: research

Impact of Tregs on AT2 Cell Transcriptomes During Resolution of ALI and Contributions of IFN- γ.
Impact of Tregs on AT2 Cell Transcriptomes During Resolution of ALI and Contributions of IFN-γ. Am J Respir Cell Mol Biol. 2020 Jun 16;: Authors: Mock JR, Dial CF, Tune MK, Gilmore RC, O'Neal WK, Dang H, Doerschuk CM Abstract By enhancing tissue repair and modulating immune responses, Foxp3+ regulatory T cells (Tregs) play essential roles in resolution from lung injury. The current study investigated the effects that Tregs exert directly or indirectly on the transcriptional profiles of type II alveolar epithelial (AT2) cells during resolution in an experimental model of acute lung injury (ALI). ...
Source: Am J Respir Cell Mol... - June 16, 2020 Category: Respiratory Medicine Authors: Mock JR, Dial CF, Tune MK, Gilmore RC, O'Neal WK, Dang H, Doerschuk CM Tags: Am J Respir Cell Mol Biol Source Type: research

New cis-acting Variants in PI*S Background Produce Null Phenotypes Causing Alpha-1 Antitrypsin Deficiency.
e S, Martinez-Delgado B Abstract Alpha-1 Antitrypsin deficiency (AATD) is an inherited condition characterized by reduced levels of serum Alpha-1 Antitrypsin (AAT) due to mutations in the SERPINA1 gene. The Pi*S (Glu264Val) is one of the most frequent deficient alleles of AATD, showing high incidence in the Iberian Peninsula. Herein, we describe two new alleles carrying S mutation, but producing null phenotype: QOVigo and QOAachen. The new alleles were identified by sequencing SERPINA1 gene in three patients who had lower AAT serum levels than expected for the initial genotype. These alleles are the result of comb...
Source: Am J Respir Cell Mol... - June 9, 2020 Category: Respiratory Medicine Authors: Matamala N, Gomez-Mariano G, Perez JA, Baladrón B, Torres-Durán M, Michel FJ, Saez R, Hernández-Pérez JM, Belmonte I, Rodriguez-Frias F, Blanco I, Strnad P, Janciauskiene S, Martinez-Delgado B Tags: Am J Respir Cell Mol Biol Source Type: research

The Intricate Web of Phospholipase A2s and Specific Features of Airway Hyperresponsiveness in Asthma.
PMID: 32484733 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - June 2, 2020 Category: Respiratory Medicine Authors: Murphy RC, Altemeier WA, Lai Y, Hallstrand TS Tags: Am J Respir Cell Mol Biol Source Type: research

Reply to: The Intricate Web of Phospholipase A2s and Specific Features of Airway Hyperresponsiveness in Asthma.
PMID: 32484747 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - June 2, 2020 Category: Respiratory Medicine Authors: Ueno H, Koya T Tags: Am J Respir Cell Mol Biol Source Type: research

α-Tocopherol Transfer Protein Enhances α-Tocopherol Protective Effects in Lung A549 Cells.
α-Tocopherol Transfer Protein Enhances α-Tocopherol Protective Effects in Lung A549 Cells. Am J Respir Cell Mol Biol. 2020 Jun;62(6):810-813 Authors: Tamura T, Otulakowski G, Post M, Kavanagh BP PMID: 32469275 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 30, 2020 Category: Respiratory Medicine Authors: Tamura T, Otulakowski G, Post M, Kavanagh BP Tags: Am J Respir Cell Mol Biol Source Type: research

Airway Hyperresponsiveness Is Severe and Persistent in an Equine Model of Neutrophilic Asthma.
PMID: 32469276 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 30, 2020 Category: Respiratory Medicine Authors: Hunter CL, Bowser JE, Wills RW, Byars P, Moore JW, Wilson RM, Byrne R, Swiderski CE Tags: Am J Respir Cell Mol Biol Source Type: research

June Highlights/Papers by Junior Investigators/NIH News.
Authors: PMID: 32469277 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 30, 2020 Category: Respiratory Medicine Tags: Am J Respir Cell Mol Biol Source Type: research

ENDS Aerosol-induced Cell Death and Dysfunction in Macrophages and Lung Epithelial Cells.
Abstract Electronic nicotine delivery system (ENDS) usage is outpacing our understanding of its potential harmful effects. Homeostasis of the lung is maintained through proper balance of cell death, efferocytic clearance, and phagocytosis of pathogens. To investigate whether ENDS use has the potential to alter this balance, we developed physiologically relevant ENDS exposure paradigms for lung epithelial cells and primary macrophages. In our studies, cells were exposed directly to aerosol made from carefully controlled components with and without nicotine. We found that ENDS aerosol exposure led to apoptosis, seco...
Source: Am J Respir Cell Mol... - May 29, 2020 Category: Respiratory Medicine Authors: Serpa GL, Renton ND, Lee N, Crane MJ, Jamieson AM Tags: Am J Respir Cell Mol Biol Source Type: research

IL-13R α2 Glycosylation Holds the Dance Card for Partnering with IL-13.
IL-13Rα2 Glycosylation Holds the Dance Card for Partnering with IL-13. Am J Respir Cell Mol Biol. 2020 May 27;: Authors: Dy ABC, Ledford JG PMID: 32459972 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 27, 2020 Category: Respiratory Medicine Authors: Dy ABC, Ledford JG Tags: Am J Respir Cell Mol Biol Source Type: research

Exploring New Therapeutic Pathways in Pulmonary Hypertension: Metabolism, Proliferation, and Personalized Medicine.
Abstract In this State-of-the-Field article, we explore the main themes from the 62nd Annual Aspen Lung Conference: hypoxia, cellular metabolism, inflammatory pathways, aberrant proliferation, and personalized medicine, and highlight challenges and opportunities in the coming decade of pulmonary vascular disease. PMID: 32453969 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 26, 2020 Category: Respiratory Medicine Authors: George MP, Gladwin MT, Graham BB Tags: Am J Respir Cell Mol Biol Source Type: research

Am J Respir Cell Mol Biol; +24 new citations
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Respir Cell Mol Biol These pubmed results were generated on 2020/05/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 13, 2020 Category: Respiratory Medicine Tags: Report Source Type: research

APOE in Asthmatic Inflammatory Response: Friend or Foe?
PMID: 32383998 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 8, 2020 Category: Respiratory Medicine Authors: Qin S, Pu Q, Wang Z, Wu M Tags: Am J Respir Cell Mol Biol Source Type: research

Am J Respir Cell Mol Biol; +17 new citations
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Respir Cell Mol Biol These pubmed results were generated on 2020/05/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - May 7, 2020 Category: Respiratory Medicine Tags: Report Source Type: research

Am J Respir Cell Mol Biol; +19 new citations
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Respir Cell Mol Biol These pubmed results were generated on 2020/04/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 29, 2020 Category: Respiratory Medicine Tags: Report Source Type: research

CD70 Activation Decreases Pulmonary Fibroblast Production of Extracellular Matrix Proteins.
Abstract Idiopathic pulmonary fibrosis (IPF) is a lethal, medically refractory syndrome characterized by intrapulmonary accumulations of extracellular matrix (ECM) proteins produced by fibroblasts. Activation, clonal expansions, and differentiation of lymphocytes are also frequently present in IPF. Activated T-cells are known to exert several effects that promote ECM production, but opposing homeostatic actions, wherein T-cells can inhibit fibrosis, are less well understood. We found CD27, a TNF receptor ubiquitously expressed on naïve T-cells, is downregulated on CD4 T-cells of IPF patients and CD70, the sol...
Source: Am J Respir Cell Mol... - April 22, 2020 Category: Respiratory Medicine Authors: Tran-Nguyen TK, Xue J, Feghali-Bostwick C, Sciurba FC, Kass DJ, Duncan SR Tags: Am J Respir Cell Mol Biol Source Type: research

The Airway Epithelial Response to Air Pollution: It's Not Just Inflammation.
PMID: 32311285 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 20, 2020 Category: Respiratory Medicine Authors: Hamanaka RB, Mutlu GM Tags: Am J Respir Cell Mol Biol Source Type: research

Am J Respir Cell Mol Biol; +33 new citations
33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Respir Cell Mol Biol These pubmed results were generated on 2020/04/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 10, 2020 Category: Respiratory Medicine Tags: Report Source Type: research

4PBA Restores Signalling of a Cysteine-substituted Mutant BMPR2 Receptor Found in Patients with PAH.
Abstract Mutations in the gene encoding the bone morphogenetic protein type 2 receptor, BMPR2, are the major cause of heritable pulmonary arterial hypertension (HPAH). Point mutations in the BMPR2 ligand binding domain involving cysteine residues (such as C118W) are causative of PAH and predicted to cause protein misfolding. Using heterologous overexpression systems, we showed previously that these mutations lead to retention of BMPR2 in the endoplasmic reticulum, but are partially rescued by chemical chaperones. Here we determine whether the chemical chaperone, 4-PBA, restores BMPR2 signalling in primary cells an...
Source: Am J Respir Cell Mol... - April 7, 2020 Category: Respiratory Medicine Authors: Dunmore BJ, Yang X, Crosby A, Moore S, Long L, Huang C, Southwood M, Austin ED, Rana A, Upton PD, Morrell NW Tags: Am J Respir Cell Mol Biol Source Type: research

Alpha-tocopherol Attenuates the Severity of Pseudomonas aeruginosa-induced Pneumonia.
Abstract Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The Type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen including increased lung permeability in a toll-like receptor 4/Rho A/plasminogen activator inhibitor (PAI)-1-dependent manner. Alpha-tocopherol has anti-inflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, Rho A and PAI-1 activation, stress fiber...
Source: Am J Respir Cell Mol... - April 3, 2020 Category: Respiratory Medicine Authors: Wagener BM, Anjum N, Evans C, Brandon A, Honavar J, Creighton J, Traber MG, Stuart RL, Stevens T, Pittet JF Tags: Am J Respir Cell Mol Biol Source Type: research

Erratum: Preferential Generation of 15-HETE-PE Induced by IL-13 Regulates Goblet Cell Differentiation in Human Airway Epithelial Cells.
Authors: PMID: 32233870 [PubMed - in process] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 1, 2020 Category: Respiratory Medicine Tags: Am J Respir Cell Mol Biol Source Type: research

April Highlights/Papers by Junior Investigators/NIH News.
Authors: PMID: 32233871 [PubMed - in process] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 1, 2020 Category: Respiratory Medicine Tags: Am J Respir Cell Mol Biol Source Type: research

Asthma - An Untoward Consequence of Endurance Sports?
circ;té A PMID: 32223717 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - March 30, 2020 Category: Respiratory Medicine Authors: Bossé Y, Côté A Tags: Am J Respir Cell Mol Biol Source Type: research

A Fresh Take on the "TCA" Cycle: TETs, Citrate, and Asthma.
A Fresh Take on the "TCA" Cycle: TETs, Citrate, and Asthma. Am J Respir Cell Mol Biol. 2020 Mar 30;: Authors: Huang S PMID: 32223718 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - March 30, 2020 Category: Respiratory Medicine Authors: Huang S Tags: Am J Respir Cell Mol Biol Source Type: research

The Transient Receptor Potential Channel Vanilloid 1 (TRPV1) is Critical in Innate Airway Epithelial Responses to Protease Allergens.
Abstract The airway epithelium plays a critical role in innate responses to airborne allergens by secreting IL-1 family cytokines such as interleukin (IL)-1α and IL-33, as alarmins that subsequently orchestrate appropriate immune responses. Previous studies revealed that epithelial IL-33 secretion by allergens such as A. alternaria (ALT) or house dust mite (HDM) involves Ca2+-dependent signaling, via initial activation of ATP-stimulated type 2 purinoceptors (P2YR2) and subsequent activation of the NADPH oxidase DUOX1. We sought to identify proximal mechanisms by which epithelial cells sense these allergens, ...
Source: Am J Respir Cell Mol... - March 17, 2020 Category: Respiratory Medicine Authors: Schiffers C, Hristova M, Habibovic A, Dustin CM, Danyal K, Reynaert NL, Wouters EFM, van der Vliet A Tags: Am J Respir Cell Mol Biol Source Type: research

Cysteinyl Leukotriene synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling.
CONCLUSION: These data suggested that AHR and airway remodeling was caused by repeated and strenuous exercise. Cys-LTs from the airway epithelium but not inflammatory cells may play an important role in this mouse model. PMID: 32182104 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - March 17, 2020 Category: Respiratory Medicine Authors: Ueno H, Koya T, Takeuchi H, Tsukioka K, Saito A, Kimura Y, Hayashi M, Watanabe S, Hasegawa T, Arakawa M, Kikuchi T Tags: Am J Respir Cell Mol Biol Source Type: research

Vitamin D: Feel it in More Than Just Your Bones!
PMID: 32160008 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - March 11, 2020 Category: Respiratory Medicine Authors: Cornfield DN Tags: Am J Respir Cell Mol Biol Source Type: research

Basement Membrane Remodelling Controls Endothelial Function in IPAH.
Abstract The extracellular matrix (ECM) increasingly emerges as an active driver in several diseases, including idiopathic pulmonary arterial hypertension (IPAH). The basement membrane (BM) is a specialized class of ECM proteins. In pulmonary arteries, the BM is in close contact and direct proximity to vascular cells including endothelial cells. So far, the role of the BM has remained under-investigated in IPAH. Here, we aimed to shed light on the involvement of the BM in IPAH, by addressing its structure, composition and function. On an ultrastructural level, we observed a marked increase in BM thickness in IPAH ...
Source: Am J Respir Cell Mol... - March 11, 2020 Category: Respiratory Medicine Authors: Jandl K, Marsh LM, Hoffmann J, Mutgan AC, Baum O, Bloch W, Thekkekara-Puthenparampil H, Kolb D, Sinn K, Klepetko W, Heinemann A, Olschewski A, Olschewski H, Kwapiszewska G Tags: Am J Respir Cell Mol Biol Source Type: research

Macrophage Signaling Pathways in Pulmonary Nontuberculous Mycobacteria Infections.
Abstract The incidence and prevalence of nontuberculous mycobacterial lung disease (NTM-LD) is rising worldwide and accounts for most clinical cases of NTM. NTM infections occur in both immunocompetent and immunocompromised hosts. Macrophages are the primary host cells that initiate an immune response to NTM. Defining the molecular events that govern the control of infection within macrophages is fundamental to understanding the pathogenesis of NTM disease. Here, we review key macrophage host signaling pathways that contribute to the host immune response to pulmonary NTM infections. In this review, we focus primar...
Source: Am J Respir Cell Mol... - March 11, 2020 Category: Respiratory Medicine Authors: Prasla Z, Sutliff RL, Sadikot RT Tags: Am J Respir Cell Mol Biol Source Type: research

Maternal Vitamin D Deficiency Causes Sustained Impairment of Lung Structure and Function and Increases Susceptibility to Hyperoxia-Induced Lung Injury in Infant Rats.
CONCLUSIONS: Maternal VDD causes abnormal airway, alveolar and vascular growth, as well as impaired lung function and airways hyper-reactivity in infancy. In addition, VDD pups were more susceptible for worsened lung structure and function after exposure to hyperoxia after birth. We speculate that fetal disruption of VD signaling impairs airway and distal lung structure and function during infancy, and risk for late respiratory disease. PMID: 32135073 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - March 5, 2020 Category: Respiratory Medicine Authors: Mandell EW, Ryan S, Seedorf GJ, Gonzalez T, Smith BJ, Fleet JC, Abman SH Tags: Am J Respir Cell Mol Biol Source Type: research

"T"eeing Up A Novel Therapy for Lymphangioleiomyomatosis.
"T"eeing Up A Novel Therapy for Lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 2020 Feb 26;: Authors: Wang X, Rojas-Quintero J, Owen CA PMID: 32101457 [PubMed - as supplied by publisher] (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - February 26, 2020 Category: Respiratory Medicine Authors: Wang X, Rojas-Quintero J, Owen CA Tags: Am J Respir Cell Mol Biol Source Type: research

Serine Protease Imbalance in the Small Airways and Development of Centrilobular Emphysema in COPD.
This study aimed to show the roles of C/EBPα in the distal airway during chronic cigarette smoke (CS) exposure in mice and in the small airways in smokers. In a model of chronic smoke exposure using epithelial cell-specific C/EBPα-knockout mice, significant pathological phenotypes, such as higher protease activity, impaired ciliated cell regeneration, epithelial cell barrier dysfunction via reduced Zo-1, and decreased alveolar attachments, were found in C/EBPα-knockout mice compared to control mice. We found that Spink5 gene (encoding Lympho-epithelial Kazal-type-related inhibitor (LEKTI), an anti-serine ...
Source: Am J Respir Cell Mol... - February 26, 2020 Category: Respiratory Medicine Authors: Uemasu K, Tanabe N, Tanimura K, Hasegawa K, Mizutani T, Hamakawa Y, Sato S, Ogawa E, Thomas MJ, Ikegami M, Muro S, Hirai T, Sato A Tags: Am J Respir Cell Mol Biol Source Type: research