A Dynamic Bronchial Airway Gene Expression Signature of COPD and Lung Function Impairment The authors report that in silico analysis identified ATF4 as a potential transcriptional regulator of genes with COPD-associated airway expression, and ATF4 overexpression in airway epithelial cells in vitro recapitulates COPD-associated gene expression changes. [Am J Resp Crit Care] Abstract Anti-Inflammatory Role of PGD2 in Acute Lung Inflammation and Therapeutic Application of Its Signal Enhancement Scientists report that data obtained from bone marrow transplantation between WT and prostaglandin D2 (PGD2) receptor, DP-deficient mice suggest that the DP signal in alveolar endothelial cells is crucial for the anti-inflammatory reactions of PGD2. In vitro, DP agonism directly enhanced endothelial barrier formation, and 15-deoxy-Δ12,14-PGJ2 attenuated both neutrophil migration and cytokine expression. [Proc Natl Acad Sci USA] Abstract IL-22 Is Essential for Lung Epithelial Repair Following Influenza Infection Wild-type and IL-22−/− mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22−/− mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. [Am J Pathol] Abstract Discrimination between Lung Homeostatic and Injury-Induced Epithelial Progenitor Subsets by Cell-Density Properties To enhance current methods of lung stem cell isolation and identification and to investigate biophysical changes which occur during homeostasis and in response to acute lung injury, investigators separated cells on a discontinuous density gradient and characterized the eluted lineages. [Stem Cells Dev] Abstract Muramyl Dipeptide Mediated Activation of Human Bronchial Epithelial Cells Interacting with Basophils: A Novel Mechanism of Airway Inflammation Researchers investigated activation of the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) ligand muramyl dipeptide on primary human bronchial epithelial cells (HBE) co-cultured with human basophils. Cytokines, NOD2, adhesion molecules and intracellular signaling molecules were assayed by enzyme-linked immunosorbent assay or flow cytometry. The protein expression of NOD2 was confirmed in basophils/KU812 cells and HBE/human bronchial epithelial cell line cells. [Clin Exp Immunol] Abstract LUNG CANCER An Endogenous Inhibitor of Angiogenesis Inversely Correlates with Side Population Phenotype and Function in Human Lung Cancer Cells Scientists examined the hypothesis that the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) antitumor activity may involve regulation of the side population (SP) in human lung cancer cells. Indeed, using Hoechst dye efflux assay and flow cytometry, as well as quantitative reverse transcriptase-PCR analysis, they found that endogenous TIMP-2 mRNA levels showed a significant inverse correlation with SP fraction size in six non-small cell lung cancer cell lines. [Oncogene] Abstract Downregulation of miR-486-5p Contributes to Tumor Progression and Metastasis by Targeting Protumorigenic ARHGAP5 in Lung Cancer Researchers evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of non-small-cell lung cancer (NSCLC) by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. They then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues, and associated with stage and lymph node metastasis of NSCLC. [Oncogene] Abstract Protein Phosphorylation Profiling Using an In Situ Proximity Ligation Assay: Phosphorylation of AURKA-Elicited EGFR-Thr654 and EGFR-Ser1046 in Lung Cancer Cells The epidermal growth factor receptor (EGFR), which is up-regulated in lung cancer, involves the activation of mitogenic signals and triggers multiple signaling cascades. To dissect these EGFR cascades, scientists used 14 different phospho-EGFR antibodies to quantify protein phosphorylation using an in situ proximity ligation assay. Phosphorylation at EGFR-Thr654 and -Ser1046 was EGF-dependent in the wild-type receptor but EGF-independent in a cell line carrying the EGFR-L858R mutation. [PLoS One] Full Article Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines There have been indications that lung cancer is propagated and maintained by a small population of cancer stem cells (CSCs). To study this question researchers established a panel of 15 primary lung cancer cell lines from 20 fresh primary tumors using a robust serum-free culture system. They subsequently focused on identification of lung CSCs by studying these cell lines derived from four representative lung cancer subtypes such as small cell lung cancer, large cell carcinoma, squamous cell carcinoma and adenocarcinoma. [PLoS One] Full Article DNA Adducts in Aldehyde Dehydrogenase-Positive Lung Stem Cells of A/J Mice Treated with the Tobacco Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) Aldehyde dehydrogenase (ALDH) is a marker of stem cells. To investigate the presence of DNA modifications in these cells, researchers isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen NNK. Using LC-NSI-HRMS/MS-PRM, O6-methyl-G, 7-POB-G and O2-POB-dT were positively identified in ALDH-positive cell DNA. [Chem Res Toxicol] Abstract |