C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation

Richter, Katrin; Sagawe, Sabrina; Hecker, Andreas; Küllmar, Mira; Askevold, Ingolf; Damm, Jelena; Heldmann, Sarah; Pöhlmann, Michael; Ruhrmann, Sophie; Sander, Michael; Schlüter, K.-D.; Wilker, Sigrid; König, Inke R.; Kummer, Wolfgang; Padberg, Winfried; Hone, Arik J.; McIntosh, J. Michael; Zakrzewicz, Anna; Koch, Christian; Grau, Veronika

doi:10.3389/fimmu.2018.01604

Cited by 45 publications

(72 citation statements)

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“…For example, activation of nAChR in monocytes inhibits ATP-induced inflammasome activation by inhibiting IL1β-release. 14,51,52 In conclusion, the present findings reveal that the whole transcriptome of tracheal epithelial BC is distinct to that | 331 HOLLENHORST ET aL. of ciliated cells.…”

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confidence: 52%

“…In our study the acute inhibition of M2R in the trachea almost doubled the increase in PTS after stimulation of brush cells with bitter tasting substances. 14,51,52 In conclusion, the present findings reveal that the whole transcriptome of tracheal epithelial BC is distinct to that | 331 HOLLENHORST ET aL. 16 Additionally, ACh mediates important innate immune functions after being released from BC, for example, induction of protective respiratory reflexes.…”

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confidence: 67%

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Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

et al. 2019

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This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. AbstractFor protection from inhaled pathogens many strategies have evolved in the airways such as mucociliary clearance and cough. We have previously shown that protective respiratory reflexes to locally released bacterial bitter "taste" substances are most probably initiated by tracheal brush cells (BC). Our single-cell RNA-seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (Tas2r108, Gnat3, Trpm5). We directly demonstrate the secretion of acetylcholine (ACh) from BC upon stimulation with the Tas2R agonist denatonium. Inhibition of the taste transduction cascade abolished the increase in [Ca 2+ ] i in | 317 HOLLENHORST ET aL.

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confidence: 52%

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confidence: 67%

Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

et al. 2019

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“…[V11L, V16D]ArIB and RgIA4 were produced and characterized as described previously [ 5 , 7 , 43 , 44 , 45 ]. Concentrations of all compounds used in this study were optimized in previous experiments on human monocytic U937 cells [ 6 , 7 , 8 , 11 , 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, PC is a ligand of the pentraxin C-reactive protein (CRP), an acute phase protein present in human blood that is a widely used clinical marker for inflammation [ 9 , 10 ]. We found that endogenous CRP-PC complexes are potent nAChR agonists that also inhibit the ATP-dependent inflammasome assembly and IL-1β release by human monocytic cells, whereas PC-free CRP is ineffective [ 11 ]. Moreover, we discovered that dipalmitoyl phosphatidylcholine (DPPC) and metabolites of phosphatidylcholines such as lysophosphatidylcholine or glycerophosphocholine (GPC) also function as nAChR agonists [ 8 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release

Richter

Ogiemwonyi-Schaefer

Wilker

et al. 2020

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Amyloid-β peptide (Aβ1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of the nervous system. Known interaction partners of Aβ1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aβ1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1β by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aβ1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aβ1-42. IL-1β concentrations were measured in the supernatant. Aβ1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1β-release by monocytic cells, whereas reverse Aβ42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aβ1-42 function that enables monocytic IL-1β release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aβ1-42 in the context of sterile systemic inflammation.

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“…Inversely, the expansion may limit excessive cell damage during inflammation. In humans, the acute phase protein CRP contains inflammation as part of a negative feedback loop [135]. Thus, the round goby may re-enter homeostasis faster compared to other fish species with smaller CRP/APCS repertoires.…”

Section: Response To the Environmentmentioning

confidence: 99%

The round goby genome provides insights into mechanisms that may facilitate biological invasions

et al. 2020

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Background: The invasive benthic round goby (Neogobius melanostomus) is the most successful temperate invasive fish and has spread in aquatic ecosystems on both sides of the Atlantic. Invasive species constitute powerful in situ experimental systems to study fast adaptation and directional selection on short ecological timescales and present promising case studies to understand factors involved the impressive ability of some species to colonize novel environments. We seize the unique opportunity presented by the round goby invasion to study genomic substrates potentially involved in colonization success. Results: We report a highly contiguous long-read-based genome and analyze gene families that we hypothesize to relate to the ability of these fish to deal with novel environments. The analyses provide novel insights from the large evolutionary scale to the small species-specific scale. We describe expansions in specific cytochrome P450 enzymes, a remarkably diverse innate immune system, an ancient duplication in red light vision accompanied by red skin fluorescence, evolutionary patterns of epigenetic regulators, and the presence of osmoregulatory genes that may have contributed to the round goby's capacity to invade cold and salty waters. A recurring theme across all analyzed gene families is gene expansions. Conclusions: The expanded innate immune system of round goby may potentially contribute to its ability to colonize novel areas. Since other gene families also feature copy number expansions in the round goby, and since other Gobiidae also feature fascinating environmental adaptations and are excellent colonizers, further long-read genome approaches across the goby family may reveal whether gene copy number expansions are more generally related to the ability to conquer new habitats in Gobiidae or in fish.

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C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation

Cited by 45 publications

References 67 publications

Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release

The round goby genome provides insights into mechanisms that may facilitate biological invasions

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