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Hydrated magnesium silicate (or "talc" particles) is a sclerosis agent commonly used in the management of malignant pleural effusions (MPE), a common symptom of metastatic diseases including lung cancers. However, the direct effects of talc particles to lung carcinoma cells, which can be found in the MPE fluids from lung cancer patients, are not fully understood. Here, we report a study of the signaling pathways that can modulate the cell death and interleukin (IL)-6 secretion induced by talc particles in human lung carcinoma cells. We found that talc-sensitive cells have higher mRNA and protein expression of phosphoinositide 3-kinase (PI3K) catalytic subunits α and β. Further experiments confirmed that modulation (inhibition or activation) of the PI3K pathway reduces or enhances cellular sensitivity to talc particles, respectively, independent of the inflammasome. By knocking down specific PI3K isoforms, we also confirmed that both PI3Kα and β mediate the observed talc effects. Our results suggest a novel role of the PI3K pathway in talc-induced cell death and IL-6 secretion in lung carcinoma cells. These cellular events are known to drive fibrosis, and thus further studies of the PI3K pathway may provide a better understanding of the mechanisms of talc sclerosis in the malignant pleural space.
This article was published in the following journal.
Name: American journal of respiratory cell and molecular biology
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A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.
Specific enzyme subunits that form the active sites of the type I and type II cyclic-AMP protein kinases. Each molecule of enzyme contains two catalytic subunits.
A forkhead box transcription factor and transcriptional activator which triggers type 1 programmed cell death (APOPTOSIS) in the absence of APOPTOSIS INHIBITING PROTEINS, including neuronal cell death induced by OXIDATIVE STRESS. It recognizes and binds to the DNA sequence 5'-(AG)TAAA(TC)A-3' and also functions in post-transcriptional regulation of the c-MYC PROTO-ONCOGENE.
Processes that translocate macromolecules across the cell envelope of gram negative bacteria, often directly into the host. These effectors modulate the defense response and thereby facilitate survival of the pathogen.
An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...
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