| Molecular Pathways of Spontaneous and TNF-{alpha}-Mediated Neutrophil Apoptosis under Intermittent Hypoxia. | |
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MedLine Citation:
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PMID: 20870895 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Apoptosis of polymorphonuclear cells (PMNs) is a fundamental mechanism to halt inflammation. It limits the lifespan of PMNs and thereby decreases tissue injury. In PMNs, unlike in other cells, hypoxia profoundly inhibits apoptosis. However, most studies investigating hypoxic effects on the functioning of PMN focus on acute or chronic sustained hypoxia. Thus, the mechanisms by which intermittent hypoxia (IH) affects PMN apoptosis are not known. Flow cytometry and Western blotting were used to evaluate mechanisms of constitutive and TNF-α-mediated PMN apoptosis in IH. The levels of NF-κB, p38 mitogen-activated protein kinase (MAPK), TNF receptor-2 (TNFR-2), intracellular IL-8 and its surface receptor CXCR2, were determined. Specific NF-κB (gliotoxin and parthenolide) and p38MAPK (SB202190) inhibitors were also used. TNF-α-mediated PMN apoptosis was concentration-dependent; low concentration increased PMN survival, whereas higher concentrations accelerated apoptosis. However, at all TNF-α concentrations, PMN survival was higher after four IH cycles than in normoxia. However, increasing the IH cycles to six abolished the pro-apoptotic/anti-apoptotic effects of TNF-α. Also, IH increased TNRF2 expression, nuclear NF-κB translocation, p38MAPK phosphorylation, and expression of IL-8 and CXCR2. The NF-κB inhibitors gliotoxin and parthenolide increased apoptosis and decreased IL-8 and CXCR2 expression. Also, the p38MAPK inhibitor SB202190 increased apoptosis and decreased IL-8 expression but had no effect on CXCR2 expression. Collectively, these findings provide insights into the mechanisms that prolong PMN survival after IH exposure and demonstrate the essential role played by NF-κB, the p38MAPK signaling pathway, and downstream genes in this process. |
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Authors:
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Larissa Dyugovskaya; Andrey Polyakov; Darrell Ginsberg; Peretz Lavie; Lena Lavie |
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Publication Detail:
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Type: Journal Article Date: 2010-09-24 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 45 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 154-62 Citation Subset: IM |
Affiliation:
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Unit of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, POB 9649, 31096, Haifa, Israel. lenal@tx.technion.ac.il. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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