Pulmonary Cell News Volume 2.26 | Jul 4 2013

Acetylcholine Leads to Signal Transducer and Activator of Transcription 1 (STAT-1) Mediated Oxidative/Nitrosative Stress in Human Bronchial Epithelial Cell Line
Scientists investigated whether acetylcholine generates oxidative/nitrosative stress in bronchial epithelial cells during airway inflammation of COPD and evaluated the effects of Tiotropium, a once-daily antimuscarinic drug, and Olodaterol, a long-acting ß2-agonist on these mechanisms. Induced sputum supernatants (ISSs) from COPD patients significantly increased the phosphorylation of STAT-1Ser727 and STAT-1Tyr701, induction of nitric oxide synthase and reactive oxygen species/Nitrotyrosine when compared with ISSs from healthy controls or healthy smokers subjects in 16-human bronchial epithelial cells. [Biochim Biophys Acta Mol Basis Dis] Abstract

Lysophosphatidic Acid Receptor 2 Deficiency Confers Protection against Bleomycin-Induced Lung Injury and Fibrosis in Mice
In human lung fibroblasts, knock down of lysophosphatidic acid (LPA) receptor 2 (LPA2) attenuated LPA-induced expression of transforming growth factor-ß (TGF-ß1), and differentiation of lung fibroblasts to myofibroblasts resulting in decreased expression of fibronectin, a-smooth muscle actin and collagen, as well as decreased activation of ERK1/2, Akt, Smad3 and p38 MAPK. Moreover, knock down of LPA2 with siRNA also mitigated TGF-ß1-induced differentiation of lung fibroblasts. [Am J Respir Cell Mol Biol] Abstract

Involvement of HIF-2a-Mediated Inflammation in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells
The authors investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. They showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6, interleukin-8, and interleukin-1ß. [Toxicol Appl Pharmacol] Abstract

Digoxin Net Secretory Transport in Bronchial Epithelial Cell Layers Is not Exclusively Mediated by P-Glycoprotein/MDR1
Researchers characterized MDR1 expression and the bidirectional transport of the common MDR1 probe ³H-digoxin in air-liquid interfaced layers of normal human bronchial epithelial cells and of the Calu-3 bronchial epithelial cell line at different passage numbers. [Eur J Pharm Biopharm] Full Article

Curcumin Protects the Developing Lung against Long-Term Hyperoxic Injury
To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAPK activation following in vitro exposure to hyperoxia for 24 hours in the presence or absence of curcumin. Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis for markers of lung injury and lung morphology. [Am J Physiol Lung Cell Mol Physiol] Abstract

LUNG CANCER

Expression of the Antimicrobial Peptide Cathelicidin in Myeloid Cells Is Required for Lung Tumor Growth
Scientists characterized the role of cathelicidin expressed in non-tumorous cells in a preclinical mouse model of tumor growth. In vitro studies with human cells showed that LL-37/hCAP-18 in macrophages is induced by soluble factors derived from cancer cells. [Oncogene] Abstract

STAT3 Upregulates miR-92a to Inhibit RECK Expression and to Promote Invasiveness of Lung Cancer Cells
Signal transducer and activator of transcription 3 (STAT3) activation is frequently found in human lung cancer and is associated with increased metastasis and reduced survival. Enforced expression of STAT3 decreases the endogenous matrix metalloproteinase inhibitor RECK protein but not mRNA level in H460 cells. [Brit J Cancer] Abstract

mTOR Inhibition Does Not Prevent Lung Adenocarcinoma-Induced Malignant Pleural Effusion
The authors investigated the impact of temsirolimus, in a murine model of malignant pleural effusion created with intrapleural injection of Lewis Lung Cancer cells. Temsirolimus did not affect the pleural fluid volume or the number of pleural tumor foci. [Respirology] Abstract

Combined Gemcitabine and CHK1 Inhibitor Treatment Induces Apoptosis Resistance in Cancer Stem Cell-Like Cells Enriched with Tumor Spheroids from a Non-Small Cell Lung Cancer Cell Line
Researchers demonstrated that a subset of cancer cells with cancer stem cell (CSC) properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell line. Treating these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell populations. [Front Med] Abstract

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For Persistent Asthma, Surveyed Pulmonologists Indicate That a Reduced Rate of Exacerbations Is One of the Greatest Unmet Needs
Decision Resources found that surveyed pulmonologists in the United States and Europe agree that a drug’s effect on reducing the exacerbation rate is one of the attributes that most influences their prescribing for persistent asthma. [Decision Resources] Press Release

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