TNF-α-Mediated Bronchial Barrier Disruption and Regulation by src-Family Kinase Activation Researchers assessed the effect of TNF-α, with or without src-family kinase inhibitor SU6656, on barrier properties and cytokine release in differentiated human bronchial epithelial cultures. [J Allergy Clin Immun] Abstract Lung Epithelial Cells Are Essential Effectors of Inducible Resistance to Pneumonia The inducibility of resistance was tested in mice with deficiencies of leukocyte lineages due to genetic deletions and in wild-type mice with leukocyte populations significantly reduced by antibodies or toxins. Surprisingly, these serial reductions in leukocyte lineages did not appreciably impair inducible resistance, but targeted disruption of toll-like receptor signaling in the lung epithelium resulted in complete abrogation of the protective effect. Isolated lung epithelial cells were also induced to kill pathogens in the absence of leukocytes. [Mucosal Immunol] Abstract Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Scientists investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. [mBio] Abstract | Full Article Lipopolysaccharide-Induced Phosphorylation of c-Met Tyrosine Residue 1003 Regulates c-Met Intracellular Trafficking and Lung Epithelial Barrier Function Scientists demonstrated that lipopolysaccharide treatment of human bronchial epithelial cells induced internalization of c-Met via phosphorylation at its tyrosine residue 1003. In addition, it induced epithelial barrier dysfunction as evidenced by a decrease in transepithelial resistance in a time-dependent manner. [Am J Physiol-Lung C] Abstract Oxidative Stress Mediates the Disruption of Airway Epithelial Tight Junctions through a TRPM2-PLCγ1-PKCα Signaling Pathway In human bronchial epithelial-16 cells, researchers demonstrated the degradation of zonula occludens-1, and claudin-2 exhibited a great dependence on the activation of the transient receptor potential melastatin (TRPM) 2 channel, phospholipase Cγ1 (PLCγ1) and the protein kinase Cα (PKCα) signaling cascade. [Int J Mol Sci] Abstract | Full Article LUNG CANCER RIP1 Potentiates Benzo[a]Pyrene Diol Epoxide-Induced Transformation in Human Bronchial Epithelial Cells through Catalase-Mediated Suppression of Excessive Reactive Oxygen Species Investigators found that receptor-interacting protein 1 (RIP1) expression is substantially increased in human non-small cell lung cancer and mouse lung tumor tissues. RIP1 expression was remarkably increased in cigarette smoke-exposed mouse lung. [Carcinogenesis] Abstract Antitumor Activity of Pimasertib, a Selective MEK 1/2 Inhibitor, in Combination with PI3K/mTOR Inhibitors or with Multi-Targeted Kinase Inhibitors in Pimasertib-Resistant Human Lung and Colorectal Cancer Cells The in vitro and in vivo anti-tumor activity of pimasertib, a selective MEK 1/2 inhibitor, alone or in combination with a PI3K inhibitor, a mTOR inhibitor, or with multi-targeted kinase inhibitors, that block also BRAF and CRAF, were tested in a panel of eight human lung and colon cancer cell lines. [Int J Cancer] Abstract TGF-β1 Exposure Induces Epithelial to Mesenchymal Transition both in CSCs and Non-CSCs of the A549 Cell Line, Leading to an Increase of Migration Ability in the CD133+ A549 Cell Fraction Scientists demonstrated that transforming growth factor-β1 (TGF-β1) induces epithelial-to-mesenchymal transition in both cancer stem cells (CSC) and non-CSC A549 sublines, upregulating the expression of mesenchymal markers such as vimentin and Slug, and downregulating levels of epithelial markers such as e-cadherin and cytokeratins. [Cell Death Dis] Full Article Metformin Inhibits Growth and Enhances Radiation Response of Non-Small Cell Lung Cancer (NSCLC) through ATM and AMPK Researchers examined the potential of metformin to enhance non-small cell lung cancer responses to ionising radiation. Metformin inhibited proliferation and radio-sensitised NSCLC cells. [Brit J Cancer] Abstract The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma Using loss of heterozygosity and array comparative genomic hybridization analyses, investigators observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. [PLoS One] Full Article |