Journal of Organic & Inorganic Chemistry

C-reactive protein has the potential to inhibit trauma-induced interleukin-1β release

C-reactive protein (CRP) is an acute phase reactant mainly produced in the liver in response to elevated levels of interleukin-1β (IL-1β) and IL-6.
Its clinical relevance as an indicator of inflammation is outstanding but the biological functions are poorly defined. CRP belongs to the family
of pentraxins and calcium-dependently binds ligands containing a phosphocholine head-group. We demonstrate that CRP isolated from human
bodily fluids is an unconventional agonist of monocytic nicotinic acetylcholine receptors (nAChR) containing subunits α7, α9 and α10. Marginally
pathologic CRP levels (IC50 = 4.9 mg/l) efficiently inhibit ATP-dependent NLRP3 inflammasome activation and IL-1β maturation by human monocytic
cells. This activity of CRP critically depends on bound phosphocholine-containing ligands. Remarkably, CRP does not trigger canonical ionotropic
nAChR functions in excitable cells but inhibits the ionotropic function of the ATP-sensitive P2X7 receptor in monocytic cells. The ATP-independent
release of IL-1β typically caused by pathogens and the release of inflammasome-independent cytokines, however, remain unimpaired. In a
prospective think around on numerous injury patients IL-1β plasma concentrations conflictingly associated with going some time recently CRP
levels, whereas inflammasome-independent cytokines earnestly associated. We suggest that CRP evolved as a negative feedback-regulator of ATPdependent
NLRP3 inflammasome activation and IL-1β release and thus, is an efficient safeguard against trauma-associated sterile inflammation.

Author(s):

Veronika Garu

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