Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Front Immunol ; 9: 1604, 2018.
Article in English | MEDLINE | ID: mdl-30105015

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-1ß (IL-1ß) and of the IL-1ß-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1ß 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-1ß maturation and secretion. Here, we demonstrate that CRP, in association with PC, efficiently reduces ATP-induced inflammasome activation and IL-1ß 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 (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-1ß 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.


Subject(s)
C-Reactive Protein/immunology , Inflammasomes/immunology , Inflammation , Adult , Aged , Biomarkers , C-Reactive Protein/pharmacology , Cells, Cultured , Cytokines/immunology , Cytokines/metabolism , Humans , Inflammasomes/metabolism , Inflammation/immunology , Inflammation/metabolism , Interleukin-1beta/immunology , Interleukin-1beta/metabolism , Male , Middle Aged , Receptors, Nicotinic/immunology , Receptors, Nicotinic/metabolism , Receptors, Purinergic P2X7/immunology , Receptors, Purinergic P2X7/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...