Pulmonary Cell News Volume 2.15 | Apr 18 2013

Type I IFN Triggers RIG-I/TLR3/NLRP3-Dependent Inflammasome Activation in Influenza A Virus Infected Cells
Investigators describe the relative roles of the host innate receptors RIG-I, TLR3, and NLRP3 in the IL-1β response to influenza A virus in primary lung epithelial cells. To activate IL-1β secretion, these cells employ partially redundant recognition mechanisms that differ from those described in macrophages. [PLoS Pathog] Full Article

IL-13-Producing BLT1-Positive CD8 Cells Are Increased in Asthma and Are Associated with Airway Obstruction
Bronchoalveolar lavage cells were obtained from asthmatic and healthy control subjects. Cells were stimulated with phorbol ester and ionomycin in the presence of brefeldin A and stained for CD8, BLT1, and intracellular IL-13. The results showed that a subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 were detected in the airways of all asthmatic subjects. [Allergy] Abstract

Changes in MicroRNA and mRNA Expression with Differentiation of Human Bronchial Epithelial Cells
Scientists studied the changes in expression of microRNAs and mRNA in normal human bronchial epithelial cells as they differentiate from an undifferentiated monolayer to a differentiated pseudostratified epithelium after 28 days of air/liquid interface (ALI) culture. After 28 days in ALI, the epithelial cells differentially expressed basal, ciliated and goblet cell markers. [Am J Resp Cell Mol] Abstract

Laminin-332 and α3β1 Integrin-Supported Migration of Bronchial Epithelial Cells is Modulated by Fibronectin
Researchers investigated the relative contributions of laminin and fibronectin to bronchiolar cell adhesion and migration using the immortalized bronchial lung epithelial cell line (BEP2D) and normal human bronchial epithelial (NHBE) cells, both of which assemble a laminin-322/fibronectin-rich matrix. Intriguingly, BEP2D and NHBE cells migrate significantly faster on a laminin-332-rich matrix than on fibronectin. [Am J Resp Cell Mol] Abstract

Identification of Stable Benzo[a]Pyrene-7,8-Dione-DNA Adducts in Human Lung Cells
Researchers studied stable DNA adduct formation of B[a]P-7,8-dione in human lung adenocarcinoma A549 cells, human bronchoalveolar H358 cells, and immortalized human bronchial epithelial HBEC-KT cells. Several stable DNA adducts of B[a]P-7,8-dione were only detected in A549 and HBEC-KT cells. [Chem Res Toxicol] Abstract

Comparative Cytoprotective Effects of Carbocysteine and Fluticasone Propionate in Cigarette Smoke Extract-Stimulated Bronchial Epithelial Cells
Investigators aimed to assess the effects of carbocysteine in cell survival and intracellular reactive oxygen species production as well as total glutathione, heme oxygenase-1, nuclear-related factor 2 expression and histone deacetylase 2 expression/activation in cigarette smoke extracts (CSE)-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate. CSE, carbocysteine or fluticasone propionate did not induce cell necrosis or cell apoptosis in 16-HBE. [Cell Stress Chaperon] Abstract

LUNG CANCER

Rewiring of Human Lung Cell Lineage and Mitotic Networks in Lung Adenocarcinomas
Gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. Scientists report that the networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. [Nat Commun] Abstract

DDX3 Loss by p53 Inactivation Promotes Tumor Malignancy via the MDM2/Slug/E-Cadherin Pathway and Poor Patient Outcome in Non-Small-Cell Lung Cancer
Scientists hypothesized that DDX3 loss by p53 inactivation may promote tumor malignancy and poor patient outcome. Mechanically, DDX3 loss by p53 knockdown and E6 overexpression was observed in A549 lung cancer cells. [Oncogene] Abstract

miR-194 Suppresses Metastasis of Non-Small Cell Lung Cancer through Regulating Expression of BMP1 and p27^kip1
Researchers showed that overexpression of microRNA-194 (miR-194) in lung cancer cell lines results in suppressing metastasis of lung cancer cells, while inhibiting its expression through ‘miRNA sponge’ promotes the cancer cells to metastasize. [Oncogene] Abstract

Bone Morphogenetic Protein Type I Receptor Antagonists Decrease Growth and Induce Cell Death of Lung Cancer Cell Lines
Investigators showed that bone morphogenetic protein (BMP) signaling is basally active in lung cancer cell lines, which can be effectively inhibited with selective antagonists of the BMP type I receptors. Lung cancer cell lines express alk2, alk3, and alk6 and inhibition of a single BMP receptor was not sufficient to decrease signaling. [PLoS One] Full Article

Fox Chase Researchers Find Some Lung Cancers Linked to Common Virus
A common virus known to cause cervical and head and neck cancers may also trigger some cases of lung cancer according to new research. Examining tissue samples from lung cancer patients, researchers found that nearly 6% showed signs they may have been driven by a strain of human papillomavirus known to cause cancer. [Press release from Fox Chase Cancer Center discussing research presented at the AACR Annual Meeting 2013, Washington] Press Release

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FDA Advisory Committee Recommends Approval of BREO(TM) ELLIPTA(TM) for the Treatment of COPD
GlaxoSmithKline plc and Theravance, Inc. announced that the Pulmonary-Allergy Drugs Advisory Committee to the US Food and Drug Administration voted that the efficacy and safety data provide substantial evidence to support approval of  BREO™ ELLIPTA™ as a once-daily inhaled treatment for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD) and also for the reduction of COPD exacerbations in patients with a history of exacerbations. [GlaxoSmithKline plc]
Press Release

Lung Cancer Foundation Charity 5K Run to Show Support for Boston
The 3rd Annual Your Next Step is the Cure 5K walk/run at Reverchon Park will honor the victims and heroes of the Boston Marathon bombing by starting with a 26-second moment of silence – one second for every mile of the marathon. The Bonnie J. Addario Lung Cancer Foundation, who hosts the event to raise funds for lung cancer awareness and research, is also encouraging runners to wear blue and yellow, the colors of the Boston Marathon. [PR Newswire Association LLC] Press Release

Savara Pharmaceuticals Initiates Phase II Clinical Trial of AeroVanc for MRSA Lung Infection in Cystic Fibrosis Patients
Savara Pharmaceuticals announced that the first patient has started study drug treatment in a Phase II clinical trial evaluating the safety and efficacy of AeroVanc for the treatment of persistent methicillin-resistant Staphylococcus aureus (MRSA) lung infection in cystic fibrosis patients. [PR Newswire Association LLC]
Press Release

National Institutes of Health (United States)

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Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Gordon Research Conference: Mucosal Health & Disease
June 9-14, 2013
Easton, United States

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