10.3389/fimmu.2018.01604.s001
Katrin Richter
Katrin
Richter
Sabrina Sagawe
Sabrina
Sagawe
Andreas Hecker
Andreas
Hecker
Mira Küllmar
Mira
Küllmar
Ingolf Askevold
Ingolf
Askevold
Jelena Damm
Jelena
Damm
Sarah Heldmann
Sarah
Heldmann
Michael Pöhlmann
Michael
Pöhlmann
Sophie Ruhrmann
Sophie
Ruhrmann
Michael Sander
Michael
Sander
Klaus-Dieter Schlüter
Klaus-Dieter
Schlüter
Sigrid Wilker
Sigrid
Wilker
Inke R. König
Inke
R. König
Wolfgang Kummer
Wolfgang
Kummer
Winfried Padberg
Winfried
Padberg
Arik J. Hone
Arik
J. Hone
J. Michael McIntosh
J. Michael
McIntosh
Anna Teresa Zakrzewicz
Anna Teresa
Zakrzewicz
Christian Koch
Christian
Koch
Veronika Grau
Veronika
Grau
Presentation_1_C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation.pdf
Frontiers
2018
C-reactive protein
interleukin-1β
NLRP3 inflammasome
monocytes
nicotinic acetylcholine receptors
sterile inflammation
2018-07-30 04:13:05
Presentation
https://frontiersin.figshare.com/articles/presentation/Presentation_1_C-Reactive_Protein_Stimulates_Nicotinic_Acetylcholine_Receptors_to_Control_ATP-Mediated_Monocytic_Inflammasome_Activation_pdf/6875774
<p>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-1β (IL-1β) and of the IL-1β-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1β levels can cause life-threatening diseases such as trauma-associated systemic inflammation. We hypothesized that CRP acts as a negative feedback regulator of monocytic IL-1β maturation and secretion. Here, we demonstrate that CRP, in association with PC, efficiently reduces ATP-induced 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 (IC<sub>50</sub> = 4.9 µg/ml). CRP elicits metabotropic functions at nicotinic acetylcholine (ACh) receptors (nAChRs) containing subunits α7, α9, and α10 and suppresses the function of ATP-sensitive P2X7 receptors in monocytic cells. Of note, CRP does not induce ion currents at conventional nAChRs, 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-1β plasma concentrations negatively correlated with preceding CRP levels, whereas inflammasome-independent cytokines IL-6, IL-18, and TNF-α positively correlated. In conclusion, PC-laden CRP is an unconventional nicotinic agonist that potently inhibits ATP-induced inflammasome activation and might protect against trauma-associated sterile inflammation.</p>