C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation
dc.contributor.author | Richter, Katrin | |
dc.contributor.author | Sagawe, Sabrina | |
dc.contributor.author | Hecker, Andreas | |
dc.contributor.author | Küllmar, Mira | |
dc.contributor.author | Askevold, Ingolf | |
dc.contributor.author | Damm, Jelena | |
dc.contributor.author | Heldmann, Sarah | |
dc.contributor.author | Pöhlmann, Michael | |
dc.contributor.author | Ruhrmann, Sophie | |
dc.contributor.author | Sander, Michael | |
dc.contributor.author | Schlüter, Klaus-Dieter | |
dc.contributor.author | Wilker, Sigrid | |
dc.contributor.author | König, Inke R. | |
dc.contributor.author | Kummer, Wolfgang | |
dc.contributor.author | Padberg, Winfried | |
dc.contributor.author | Hone, Arik J. | |
dc.contributor.author | McIntosh, J. Michael | |
dc.contributor.author | Zakrzewicz, Anna Teresa | |
dc.contributor.author | Koch, Christian | |
dc.contributor.author | Grau, Veronika | |
dc.date.accessioned | 2022-11-18T09:53:50Z | |
dc.date.available | 2019-05-20T14:57:25Z | |
dc.date.available | 2022-11-18T09:53:50Z | |
dc.date.issued | 2018 | |
dc.description.abstract | Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently measured as a clinical marker for inflammation, but the biological functions of CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin, mainly produced in the liver in response to elevated levels of interleukin-1beta (IL-1beta) and of the IL-1beta-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1beta levels can cause life-threatening diseases such as trauma-associated systemic inflammation. We hypothesized that CRP acts as a negative feed back regulator of monocytic IL-1beta maturation and secretion. Here, we demonstrate that CRP, in association with phosphocholine, efficiently reduces ATP-mediated inflammasome activation and IL-1β release from human peripheral blood mononuclear leukocytes and monocytic U937 cells. Effective concentrations are in the range of marginally pathologic CRP levels (IC50 = 4.9 µg/ml). CRP elicits metabotropic functions at nicotinic acetylcholine receptors (nAChR) containing subunits alpha7, alpha9 and alpha10 and suppresses the function of ATP-sensitive P2X7 receptors in monocytic cells. Of note, CRP does not induce ion currents at conventional nAChR, suggesting that CRP is a potent nicotinic agonist controlling innate immunity without entailing the risk of adverse effects in the nervous system. In a prospective study on multiple trauma patients, IL-1beta plasma concentrations negatively correlated with preceding CRP levels, whereas inflammasome-independent cytokines IL 6 and TNF-alpha positively correlated. In conclusion, phosphocholine-laden CRP is an unconventional nicotinic agonist that potently inhibits ATP-induced inflammasome activation and has the potential to protect against trauma-associated sterile inflammation. | en |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146319 | |
dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/9466 | |
dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-8854 | |
dc.language.iso | en | de_DE |
dc.rights | Namensnennung 4.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | C-reactive protein | en |
dc.subject | interleukin-1β | en |
dc.subject | NLRP3 inflammasome | en |
dc.subject | monocytes | en |
dc.subject | nicotinic acetylcholine receptors | en |
dc.subject.ddc | ddc:610 | de_DE |
dc.title | C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation | en |
dc.type | article | de_DE |
local.affiliation | FB 11 - Medizin | de_DE |
local.opus.fachgebiet | Medizin | de_DE |
local.opus.id | 14631 | |
local.opus.institute | Department of General and Thoracic Surgery | de_DE |
local.source.freetext | Frontiers in Immunology 9(1604) | de_DE |
local.source.uri | https://doi.org/10.3389/fimmu.2018.01604 |
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