Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S]
Interleukin (IL)-1β is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β levels, however, cause life-threatening inflammatory diseases, including systemic inflammatory response syndrome. In response to various danger signals, the pro-form of IL-1β is...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520309998 |
| _version_ | 1819055199088541696 |
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| author | Sören Backhaus Anna Zakrzewicz Katrin Richter Jelena Damm Sigrid Wilker Gabriele Fuchs-Moll Mira Küllmar Andreas Hecker Ivan Manzini Clemens Ruppert J. Michael McIntosh Winfried Padberg Veronika Grau |
| author_facet | Sören Backhaus Anna Zakrzewicz Katrin Richter Jelena Damm Sigrid Wilker Gabriele Fuchs-Moll Mira Küllmar Andreas Hecker Ivan Manzini Clemens Ruppert J. Michael McIntosh Winfried Padberg Veronika Grau |
| author_sort | Sören Backhaus |
| collection | DOAJ |
| description | Interleukin (IL)-1β is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β levels, however, cause life-threatening inflammatory diseases, including systemic inflammatory response syndrome. In response to various danger signals, the pro-form of IL-1β is synthesized and stays in the cytoplasm unless a second signal, such as extracellular ATP, activates the inflammasome, which enables processing and release of mature IL-1β. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1β. Lipopolysaccharide-primed monocytic U937 cells were stimulated with an ATP analog in the presence of natural or synthetic surfactant composed of recombinant surfactant protein (rSP)-C, palmitoylphosphatidylglycerol, and dipalmitoylphosphatidylcholine (DPPC). Both surfactant preparations dose-dependently inhibited IL-1β release from U937 cells. DPPC was the active constituent of surfactant, whereas rSP-C and palmitoylphosphatidylglycerol were inactive. DPPC was also effective in primary mononuclear leukocytes isolated from human blood. Experiments with nicotinic antagonists, siRNA technology, and patch-clamp experiments suggested that stimulation of nicotinic acetylcholine receptors (nAChRs) containing subunit α9 results in a complete inhibition of the ion channel function of ATP receptor, P2X7. In conclusion, the surfactant constituent, DPPC, efficiently inhibits ATP-induced inflammasome activation and maturation of IL-1β in human monocytes by a mechanism involving nAChRs. |
| first_indexed | 2024-12-21T13:03:43Z |
| format | Article |
| id | doaj.art-5cc171bf15eb41cc99e34af7be83f92e |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T13:03:43Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-5cc171bf15eb41cc99e34af7be83f92e2022-12-21T19:03:06ZengElsevierJournal of Lipid Research0022-22752017-06-0158610551066Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S]Sören Backhaus0Anna Zakrzewicz1Katrin Richter2Jelena Damm3Sigrid Wilker4Gabriele Fuchs-Moll5Mira Küllmar6Andreas Hecker7Ivan Manzini8Clemens Ruppert9J. Michael McIntosh10Winfried Padberg11Veronika Grau12Laboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyDepartment of Animal Physiology and Molecular Biomedicine, Justus-Liebig-University Giessen, Giessen, GermanyMedical Clinic II, Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Giessen, GermanyDepartments of Biology and Psychiatry, University of Utah and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UTLaboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyTo whom correspondence should be addressed.; Laboratory of Experimental Surgery, Department of General and Thoracic Surgery Justus-Liebig-University Giessen, Giessen, GermanyInterleukin (IL)-1β is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β levels, however, cause life-threatening inflammatory diseases, including systemic inflammatory response syndrome. In response to various danger signals, the pro-form of IL-1β is synthesized and stays in the cytoplasm unless a second signal, such as extracellular ATP, activates the inflammasome, which enables processing and release of mature IL-1β. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1β. Lipopolysaccharide-primed monocytic U937 cells were stimulated with an ATP analog in the presence of natural or synthetic surfactant composed of recombinant surfactant protein (rSP)-C, palmitoylphosphatidylglycerol, and dipalmitoylphosphatidylcholine (DPPC). Both surfactant preparations dose-dependently inhibited IL-1β release from U937 cells. DPPC was the active constituent of surfactant, whereas rSP-C and palmitoylphosphatidylglycerol were inactive. DPPC was also effective in primary mononuclear leukocytes isolated from human blood. Experiments with nicotinic antagonists, siRNA technology, and patch-clamp experiments suggested that stimulation of nicotinic acetylcholine receptors (nAChRs) containing subunit α9 results in a complete inhibition of the ion channel function of ATP receptor, P2X7. In conclusion, the surfactant constituent, DPPC, efficiently inhibits ATP-induced inflammasome activation and maturation of IL-1β in human monocytes by a mechanism involving nAChRs.http://www.sciencedirect.com/science/article/pii/S0022227520309998CHRNA7CHRNA9CHRNA10dipalmitoylphosphatidylcholineinflammasomemonocyte |
| spellingShingle | Sören Backhaus Anna Zakrzewicz Katrin Richter Jelena Damm Sigrid Wilker Gabriele Fuchs-Moll Mira Küllmar Andreas Hecker Ivan Manzini Clemens Ruppert J. Michael McIntosh Winfried Padberg Veronika Grau Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S] Journal of Lipid Research CHRNA7 CHRNA9 CHRNA10 dipalmitoylphosphatidylcholine inflammasome monocyte |
| title | Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S] |
| title_full | Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S] |
| title_fullStr | Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S] |
| title_full_unstemmed | Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S] |
| title_short | Surfactant inhibits ATP-induced release of interleukin-1β via nicotinic acetylcholine receptors[S] |
| title_sort | surfactant inhibits atp induced release of interleukin 1β via nicotinic acetylcholine receptors s |
| topic | CHRNA7 CHRNA9 CHRNA10 dipalmitoylphosphatidylcholine inflammasome monocyte |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520309998 |
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