Contribution of α7 Nicotinic Receptor to Airway Epithelium Dysfunction under Nicotine Exposure Nicotinic acetylcholine receptors (nAChRs) bind nicotine and nicotine-derived nitrosamines and thus mediate many of the tobacco-related deleterious effects in the lung. Researchers identified α7 nAChR as a key regulator of cystic fibrosis transmembrane conductance regulator in the airways. [Proc Natl Acad Sci USA] Abstract Lipoxin A4 Regulates Natural Killer Cell and Type 2 Innate Lymphoid Cell Activation in Asthma Researchers identified both natural killer (NK) cells and innate lymphoid cell type 2 (ILC2)s in human lung and peripheral blood in healthy and asthmatic subjects. NK cells were highly activated in severe asthma, were linked to eosinophilia, and interacted with autologous eosinophils to promote their apoptosis. ILC2s generated antigen-independent interleukin-13 (IL-13) in response to the mast cell product prostaglandin D2 alone and in a synergistic manner with the airway epithelial cytokines IL-25 and IL-33. [Science Transl Med] Abstract IL-1 Receptor Regulates MicroRNA-135b Expression in a Negative Feedback Mechanism during Cigarette Smoke-Induced Inflammation Investigators report that in vitro activation of the IL-1R1 pathway in mouse embryonic fibroblast (NIH3T3) and lung epithelial (FE1) cells resulted in increased microRNA-135b, which was blocked by IL-1R1 antagonists or small interfering RNA-mediated silencing of IL-1R1 expression. [J Immunol] Full Article PI3K p110γ Overexpression in Idiopathic Pulmonary Fibrosis Lung Tissue and Fibroblast Cells: In Vitro Effects of Its Inhibition Scientists assessed the expression of class I PI3K p110 isoforms in idiopathic pulmonary fibrosis (IPF) lung tissue as well as in tissue-derived fibroblast cell lines. They also investigated the in vitro effects of the selective inhibition of p110 isoforms on IPF fibroblast proliferation and fibrogenic activity. [Lab Invest] Abstract Proteomic Analysis of the NOS2 Interactome in Human Airway Epithelial Cells Scientists overexpressed Flag-tagged, catalytically-inactive nitric oxide synthase (NOS2) in A549 cells and used mass spectrometry to qualitatively identify NOS2 co-immunoprecipitating proteins. Stable isotope labeling of amino acids in cell culture was used to quantify the coordinate effects of cytokine stimulation on NOS2-protein interactions. [Nitric Oxide-Biol Ch] Abstract Linoleic Acid Metabolite Drives Severe Asthma by Causing Airway Epithelial Injury Scientists showed that extracellular 13-S-hydroxyoctadecadienoic acid induces mitochondrial dysfunction and airway epithelial apoptosis. This was associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. [Sci Rep] Full Article LUNG CANCER Notch Pathway Activity Identifies Cells with Cancer Stem Cell-Like Properties and Correlates with Worse Survival in Lung Adenocarcinoma Scientists investigated the role of Notch activity in lung adenocarcinoma utilizing a Notch GFP-reporter construct and a gamma-secretase inhibitor, which inhibits Notch pathway activity. Transduction of lung cancer cells with Notch GFP-reporter construct identified a subset of cells with high Notch activity (GFP-bright). GFP-bright cells had the ability to form more tumor spheres in serum-free media, and were able to generate both GFP-bright and GFP-dim (lower Notch activity) cell populations. [Clin Cancer Res] Abstract Klotho Sensitizes Human Lung Cancer Cell Line to Cisplatin via PI3k/Akt Pathway Investigators demonstrated that klotho could attenuate the resistance of lung cancer to cisplatin based chemotherapy and the apoptosis of the resistant cells with klotho overexpression was markedly increased. [PLoS One] Full Article Claudin-7 Increases Chemosensitivity to Cisplatin through the Up-Regulation of Caspase Pathway in Human NCI-H522 Lung Cancer Cells To investigate the role of claudin-7 in lung cancer cells after anti-cancer drug treatments, the authors transfected claudin-7 cDNA into human NCI-H522 lung cancer cells, which have no detectable expression of claudin-7 protein. Flow cytometry analysis demonstrated that cells transfected with claudin-7 had a significantly higher percentage of cell apoptosis when compared to that of vector transfected cell population. [Cancer Sci] Abstract Silence of Ezrin Modifies Migration and Actin Cytoskeleton Rearrangements and Enhances Chemosensitivity of Lung Cancer Cells In Vitro Researchers chose highly metastatic human lung carcinoma 95D cells, which highly express the ezrin proteins, as a model to examine the functional roles of ezrin in tumor suppression. An ezrin-silenced 95D cell line was established using lentivirus-mediated short hairpin RNA method. CCK-8 assay and soft agar assay analysis showed that downregulation of ezrin significantly suppressed the tumorigenicity and proliferation of 95D cells in vitro. [Mol Cell Biochem] Abstract |