Activation of α7 nicotinic acetylcholine receptors attenuates monocyte–endothelial adhesion through FUT7 inhibition

Wu, Chia-Hsien; Inoue, Tsuyoshi; Nakamura, Y.; Uni, Rie; Hasegawa, Shin; Maekawa, Hiroshi; Sugahara, Mai; Wada, Youichiro; Tanaka, Tetsuhiro; Nangaku, Masaomi; Inagi, Reiko

doi:10.1016/j.bbrc.2021.12.094

“…Most of the available literature suggest Chrna7 as the main receptor for acetylcholine 51 in the spleen, involved in the relay of vagus nerve signals to cytokine-producing macrophages via acetylcholine-synthesizing T cells in the spleen 52 and as recently discovered, this Chrna7-based activation of macrophages seems to be mediated by a downregulation of α1,3-Fucosyltransferase Fut7. 53 We could not see any upregulation of Chrna7 in spleen, however we did see a downregulation in Fut7 +3h post recall in both test and positive, hinting towards a potential involvement of the vagal system in modulating the recall of the conditioned immune reaction. And while a recent paper by Verlinden et al 2019 54 demonstrated catecholaminergic but no direct cholinergic innervation of the spleen, this finding does not rule out the possibility of an indirect vagal innervation via postganglionic non-cholinergic fibers, further supported by a recent study by Zhang et al 55 that has shown that CRH neurons originating from the CeA of the amygdala and PVN of the hypothalamus can stimulate splenic plasma cells formation via direct splenic innervation, potentially via intermediate T cells, translating the noradrenalinergic signal into an acetylcholinergic message.…”

Section: Discussionmentioning

confidence: 53%

Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study

Rueckels¹,

Picard-Mareau²

2022

F1000Res

0

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Background: Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods: Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results: In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions: Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.

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“…It has been reported that the administration of nicotine inhibits the expression of CD11b molecules on the surface of neutrophils through suppression of actin polymerization with subsequent inhibition of neutrophil recruitments. NR agonists block the interaction between monocytes and endothelial cells through suppression of the expression of adhesion molecules (Wu et al 2022 ). Moreover, NR agonists attenuate mast cell activation with the inhibition of the release of pro-inflammatory cytokines and leukotrienes.…”

Section: Cholinergic Receptors and Immune Cellsmentioning

confidence: 99%

Cholinergic dysfunction in COVID-19: frantic search and hoping for the best

Nadwa

¹

,

Al-Kuraishy

²

,

Al-Gareeb

³

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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A novel coronavirus known as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a potential cause of acute respiratory infection called coronavirus disease 2019 (COVID-19). The binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2) induces a series of inflammatory cellular events with cytopathic effects leading to cell injury and hyperinflammation. Severe SARS-CoV-2 infection may lead to dysautonomia and sympathetic storm due to dysfunction of the autonomic nervous system (ANS). Therefore, this review aimed to elucidate the critical role of the cholinergic system (CS) in SARS-CoV-2 infection. The CS forms a multi-faceted network performing diverse functions in the body due to its distribution in the neuronal and non-neuronal cells. Acetylcholine (ACh) acts on two main types of receptors which are nicotinic receptors (NRs) and muscarinic receptors (MRs). NRs induce T cell anergy with impairment of antigen-mediated signal transduction. Nicotine through activation of T cell NRs inhibits the expression and release of the pro-inflammatory cytokines. NRs play important anti-inflammatory effects while MRs promote inflammation by inducing the release of pro-inflammatory cytokines. SARS-CoV-2 infection can affect the morphological and functional stability of CS through the disruption of cholinergic receptors. SARS-CoV-2 spike protein is similar to neurotoxins, which can bind to nicotinic acetylcholine receptors (nAChR) in the ANS and brain. Therefore, cholinergic receptors mainly nAChR and related cholinergic agonists may affect the pathogenesis of SARS-CoV-2 infection. Cholinergic dysfunction in COVID-19 is due to dysregulation of nAChR by SARS-CoV-2 promoting the central sympathetic drive with the development of the sympathetic storm. As well, nAChR activators through interaction with diverse signaling pathways can reduce the risk of inflammatory disorders in COVID-19. In addition, nAChR activators may mitigate endothelial dysfunction (ED), oxidative stress (OS), and associated coagulopathy in COVID-19. Similarly, nAChR activators may improve OS, inflammatory changes, and cytokine storm in COVID-19. Therefore, nAChR activators like varenicline in virtue of its anti-inflammatory and anti-oxidant effects with direct anti-SARS-CoV-2 effect could be effective in the management of COVID-19.

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Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study

Rueckels,

Picard-Mareau

2024

F1000Res

0

View full text Add to dashboard Cite

Background: Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods: Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results: In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions: Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.

show abstract

Activation of α7 nicotinic acetylcholine receptors attenuates monocyte–endothelial adhesion through FUT7 inhibition

Cited by 4 publications

References 32 publications

Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study

Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study

Cholinergic dysfunction in COVID-19: frantic search and hoping for the best

Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study

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