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Phosphocholine-Modi...
Phosphocholine-Modified Macromolecules and Canonical Nicotinic Agonists Inhibit ATP-Induced IL-1 beta Release
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- Hecker, Andreas (author)
- University of Giessen, Germany
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- Kuellmar, Mira (author)
- University of Giessen, Germany
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- Wilker, Sigrid (author)
- University of Giessen, Germany
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- Richter, Katrin (author)
- University of Giessen, Germany; University of Giessen, Germany
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- Zakrzewicz, Anna (author)
- University of Giessen, Germany
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- Atanasova, Srebrena (author)
- University of Giessen, Germany
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- Mathes, Verena (author)
- University of Giessen, Germany
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- Timm, Thomas (author)
- University of Giessen, Germany
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- Lerner, Sabrina (author)
- University of Giessen, Germany
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- Klein, Jochen (author)
- Goethe University of Frankfurt, Germany
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- Kaufmann, Andreas (author)
- University of Marburg, Germany
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- Bauer, Stefan (author)
- University of Marburg, Germany
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- Padberg, Winfried (author)
- University of Giessen, Germany
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- Kummer, Wolfgang (author)
- University of Giessen, Germany
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- Janciauskiene, Sabina (author)
- Hannover Medical Sch, Germany
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- Fronius, Martin (author)
- University of Giessen, Germany; University of Otago, New Zealand
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- Schweda, Elke (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Lochnit, Guenter (author)
- University of Giessen, Germany
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- Grau, Veronika (author)
- University of Giessen, Germany
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(creator_code:org_t)
- 2015-09-01
- 2015
- English.
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In: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 195:5, s. 2325-2334
- Related links:
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https://www.jimmunol...
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https://urn.kb.se/re...
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https://doi.org/10.4...
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Abstract
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- IL-1 beta is a potent proinflammatory cytokine of the innate immune system that is involved in host defense against infection. However, increased production of IL-1 beta plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent detrimental collateral damage, IL-1 beta release is tightly controlled and typically requires two consecutive danger signals. LPS from Gram-negative bacteria is a prototypical first signal inducing pro-IL-1 beta synthesis, whereas extracellular ATP is a typical second signal sensed by the ATP receptor P2X7 that triggers activation of the NLRP3-containing inflammasome, proteolytic cleavage of pro-IL-1 beta by caspase-1, and release of mature IL-1 beta. Mechanisms controlling IL-1 beta release, even in the presence of both danger signals, are needed to protect from collateral damage and are of therapeutic interest. In this article, we show that acetylcholine, choline, phosphocholine, phosphocholine-modified LPS from Haemophilus influenzae, and phosphocholine-modified protein efficiently inhibit ATP-mediated IL-1 beta release in human and rat monocytes via nicotinic acetylcholine receptors containing subunits alpha 7, alpha 9, and/or alpha 10. Of note, we identify receptors for phosphocholine-modified macromolecules that are synthesized by microbes and eukaryotic parasites and are well-known modulators of the immune system. Our data suggest that an endogenous anti-inflammatory cholinergic control mechanism effectively controls ATP-mediated release of IL-1 beta and that the same mechanism is used by symbionts and misused by parasites to evade innate immune responses of the host.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hecker, Andreas
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Kuellmar, Mira
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Wilker, Sigrid
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Richter, Katrin
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Zakrzewicz, Anna
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Atanasova, Srebr ...
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show more...
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Mathes, Verena
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Timm, Thomas
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Lerner, Sabrina
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Klein, Jochen
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Kaufmann, Andrea ...
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Bauer, Stefan
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Padberg, Winfrie ...
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Kummer, Wolfgang
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Janciauskiene, S ...
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Fronius, Martin
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Schweda, Elke
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Lochnit, Guenter
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Grau, Veronika
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
- Articles in the publication
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Journal of Immun ...
- By the university
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Linköping University