Evidence for Multiple Roles for Grainyheadlike 2 in the Establishment and Maintenance of Human Mucociliary Airway Epithelium Researchers focused on the role of grainyheadlike (GRHL)2 in primary human bronchial epithelial cells, both as undifferentiated progenitors and as they differentiate in air-liquid interface culture into an organized mucociliary epithelium with transepithelial resistance. Using a dominant-negative protein or shRNA to inhibit GRHL2, they followed changes in epithelial phenotype and gene transcription using RNA sequencing or microarray analysis. [Proc Natl Acad Sci USA] Abstract | Full Article Dysregulation of Alveolar Macrophages Unleashes Dendritic Cell-Mediated Mechanisms of Allergic Airway Inflammation To understand the implication of alveolar macrophages (AM) in lung immunity, the authors investigated the influence of AM sensitization status on lung dendritic cell (DC) activation induced by allergen challenge in vivo. Rat sensitized to ovalbumin developed airway inflammation and demonstrated myeloid DC activation following allergen exposure. [Mucosal Immun] Abstract Metformin Reduces Airway Glucose Permeability and Hyperglycemia-Induced Staphylococcus aureus Load Independently of Effects on Blood Glucose Scientists investigated whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Apical S. aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia-bacteria co-culture model. [Thorax] Full Article Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells Researchers hypothesized that infiltrating eosinophils promote airway remodeling in bronchial asthma. To demonstrate this hypothesis they evaluated the effect of eosinophils on epithelial to mesenchymal transition by in vitro and in vivo studies. [PLoS One] Full Article The Activation of HMGB1 as a Progression Factor on Inflammation Response in Normal Human Bronchial Epithelial Cells through RAGE/JNK/NF-κB Pathway The inflammation response in normal human bronchial epithelial cells was stimulated by 2.5, 5, and 10 μg/ml high-mobility group box-1 (HMGB-1). However, the receptor for advanced glycation end products (RAGE) blocker RAGE-Ab or 10 μM c-Jun N-terminal kinases (JNK) inhibitor SP600125 could inhibit HMGB1-induced the release of inflammation cytokines including TNF-α, IL-8, IL-10, and MCP-1 in a dose-dependent manner. [Mol Cell Biochem] Abstract LUNG CANCER Ectopic Activation of Germline and Placental Genes Identifies Aggressive Metastasis-Prone Lung Cancers Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. Scientists designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. [Sci Transl Med] Abstract Sarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1) Investigators report the expression of PD-L1 in 13 sarcomatoid carcinomas (SCs) from two large retrospective lung cancer cohorts. Using automated quantitative immunofloresence and a mouse monoclonal antibody directed against the extracellular domain of PD-L1, they showed that 9 of 13 patients with SCs are positive for PD-L1 and their levels are higher than in conventional non-small-cell lung carcinoma. [J Thorac Oncol] Abstract Involvement of Intermediate Filament Nestin in Cell Growth of Small-Cell Lung Cancer Researchers investigated the expression and function of nestin in small-cell lung cancer (SCLC). Nestin was expressed in nine of ten SCLC cell lines. The nestin expression level was significantly higher in SCLC cell lines than in NSCLC cell lines. [Lung Cancer] Abstract The MicroRNA-200 Family Targets Multiple Non-Small Cell Lung Cancer Prognostic Markers in H1299 Cells and BEAS-2B Cells Scientists investigated whether the microRNA-200 (miR-200) family regulates our previously identified non-small cell lung cancer prognostic marker genes associated with metastasis, as potential molecular targets. Reinforced miR-200b expression results in downregulation of DLC1, HNRNPA3 and HFE. Additionally, miR-200 family downregulates HNRNPR3, HFE and ATRX in BEAS-2B immortalized lung epithelial cells in quantitative RT-PCR and western blot assays. [Int J Oncol] Abstract PRC2 Overexpression and PRC2-Target Gene Repression Relating to Poorer Prognosis in Small Cell Lung Cancer Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. Treatment with EZH2 inhibitors, DZNep and GSK126, resulted in growth repression of SCLC cell lines. [Sci Rep] Full Article |