| Elevated CO2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage. | |
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MedLine Citation:
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PMID: 20181940 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Elevated blood and tissue CO(2), or hypercapnia, is common in severe lung disease. Patients with hypercapnia often develop lung infections and have an increased risk of death following pneumonia. To explore whether hypercapnia interferes with host defense, we studied the effects of elevated P(CO2) on macrophage innate immune responses. In differentiated human THP-1 macrophages and human and mouse alveolar macrophages stimulated with lipopolysaccharide (LPS) and other Toll-like receptor ligands, hypercapnia inhibited expression of tumor necrosis factor and interleukin (IL)-6, nuclear factor (NF)-kappaB-dependent cytokines critical for antimicrobial host defense. Inhibition of IL-6 expression by hypercapnia was concentration dependent, rapid, reversible, and independent of extracellular and intracellular acidosis. In contrast, hypercapnia did not down-regulate IL-10 or interferon-beta, which do not require NF-kappaB. Notably, hypercapnia did not affect LPS-induced degradation of IkappaB alpha, nuclear translocation of RelA/p65, or activation of mitogen-activated protein kinases, but it did block IL-6 promoter-driven luciferase activity in mouse RAW 264.7 macrophages. Elevated P(CO2) also decreased phagocytosis of opsonized polystyrene beads and heat-killed bacteria in THP-1 and human alveolar macrophages. By interfering with essential innate immune functions in the macrophage, hypercapnia may cause a previously unrecognized defect in resistance to pulmonary infection in patients with advanced lung disease. |
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Authors:
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Naizhen Wang; Khalilah L Gates; Humberto Trejo; Silvio Favoreto; Robert P Schleimer; Jacob I Sznajder; Greg J Beitel; Peter H S Sporn |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-02-24 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 24 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-01 Completed Date: 2010-08-03 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 2178-90 Citation Subset: IM |
Affiliation:
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Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 240 E. Huron St., Chicago, IL 60611, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbon Dioxide / pharmacology* Cell Line, Tumor Cytokines / biosynthesis Humans Hypercapnia / immunology* Immunity, Innate / drug effects Interleukin-6 / antagonists & inhibitors*, biosynthesis Macrophages, Alveolar / drug effects, immunology* Mice Phagocytosis / drug effects* Tumor Necrosis Factor-alpha / antagonists & inhibitors*, biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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HL068546/HL/NHLBI NIH HHS; HL072891/HL/NHLBI NIH HHS; HL078860/HL/NHLBI NIH HHS; HL085534/HL/NHLBI NIH HHS; R01 AI072570-05/AI/NIAID NIH HHS; R01 HL078860-06/HL/NHLBI NIH HHS; R01 HL085534-06/HL/NHLBI NIH HHS; R37 HL068546-28/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 124-38-9/Carbon Dioxide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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