Thrombin-Induced CCAAT/Enhancer-Binding Protein β Activation and IL-8/CXCL8 Expression via MEKK1, ERK, and p90 Ribosomal S6 Kinase 1 in Lung Epithelial Cells Scientists investigated the role of the MEK kinase (MEKK)1/ERK/p90 ribosomal S6 kinase-1-dependent C/EBPβ signaling pathway in thrombin-induced IL-8/CXCL8 expression. Thrombin-induced IL-8/CXCL8 release and IL-8/CXCL8-luciferase activity were attenuated by small interfering RNA of C/EBPβ and by cells transfected with the C/EBPβ site mutation of the IL-8/CXCL8 construct. [J Immunol] Abstract A Transcriptomic Approach to Elucidate the Physiological Significance of Human Cytochrome P450 2S1 in Bronchial Epithelial Cells Two human bronchial epithelial cells were constructed to represent chronic depletion of cytochrome P450 2S1 (CYP2S1) using short-hairpin RNA (shRNA) silencing directed toward the 3’UTR and exon 3 of the CYP2S1 gene and compared with a non-targeting shRNA control. [BMC Genomics] Abstract | Full Article Thrombin Increases Lung Fibroblast Survival while Promoting Alveolar Epithelial Cell Apoptosis via the ER Stress Marker CHOP Researchers observed that thrombin, which is over-expressed in scleroderma and other interstitial lung diseases, increases the expression of CCAAT enhancer-binding homologous protein (CHOP) in primary alveolar epithelial cells and in A549 cells via an Ets1-dependent pathway. [Am J Respir Cell Mol Biol] Abstract The Impact of Allergic Rhinitis and Asthma on Human Nasal and Bronchial Epithelial Gene Expression Researchers defined gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examined the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. [PLoS One] Full Article Cross-Linking of Thioredoxin Reductase by the Sulfur Mustard Analog Mechlorethamine (Methyl Bis[2-Chloroethyl] Amine) in Human Lung Epithelial Cells and Rat Lung: Selective Inhibition of Disulfide Reduction but Not Redox Cycling Investigators report that mechlorethamine inhibits the cytosolic thioredoxin reductase(TrxR)1 and mitochondrial (TrxR2) forms of TrxR in A549 lung epithelial cells. [Chem Res Toxicol] Abstract LUNG CANCER Gefitinib Resistance Resulted from STAT3-Mediated Akt Activation in Lung Cancer Cells Scientists discovered a STAT3-dependent Akt activation that impairs the efficacy of gefitinib. Mechanistically, gefitinib increased association of EGFR with STAT3, which de-repressed STAT3 from SOCS3, an upstream suppressor of STAT3. Such a de-repression of STAT3 in turn fostered Akt activation. Genetic or pharmacological inhibition of STAT3 abrogated Akt activation and combined gefitinib with STAT3 inhibition synergistically reduced the growth of the tumor cells. [Oncotarget] Abstract [6]-Shogaol Inhibits Growth and Induces Apoptosis of Non-Small Cell Lung Cancer Cells by Directly Regulating Akt1/2 Researchers revealed that ginger components, including [6]-shogaol, [6]-paradol and [6]-gingerol, appear to be potential candidates for the prevention and treatment of non-small cell lung cancer (NSCLC). Among the compounds, [6]-shogaol showed the greatest inhibitory effects on the NSCLC cell proliferation and anchorage-independent growth. [Carcinogenesis] Abstract PA28gamma Emerges as a Novel Functional Target of Tumor Suppressor MicroRNA-7 in Non-Small-Cell Lung Cancer Researchers found that the expression of microRNA-7 was significantly downregulated not only in non-small-cell lung cancer (NSCLC) cell lines, but also in human NSCLC tissues compared with the matched adjacent tissues. [Brit J Cancer] Abstract Plumbagin Induces Apoptotic and Autophagic Cell Death through Inhibition of the PI3K/Akt/mTOR Pathway in Human Non-Small Cell Lung Cancer Cells Researchers found that plumbagin (PLB) has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. [Cancer Lett] Abstract Arsenite Evokes IL-6 Secretion, Autocrine Regulation of STAT3 Signaling, and miR-21 Expression, Processes Involved in the EMT and Malignant Transformation of Human Bronchial Epithelial Cells Scientists showed that, evoked by arsenite, secretion of interleukin-6 (IL-6) led to the activation of STAT3 and to increased levels of a microRNA, miR-21. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for three days, the arsenite-induced epithelial-mesenchymal transition (EMT) and malignant transformation were reversed. [Toxicol Appl Pharmacol] Abstract |