Physiological functions of the cholinergic system in immune cells

Fujii, Takeshi; Mashimo, Masato; Moriwaki, Yuji; Misawa, Hidemi; Ono, Shiro; Horiguchi, Kotaro; Kawashima, Koichiro

doi:10.1016/j.jphs.2017.05.002

Cited by 157 publications

(145 citation statements)

References 192 publications

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“…ChAT proteins were detected as multiple bands between 67-72 kDa with higher molecular weights in Sham and ConA + Sham groups than those in corresponding hVNSadministered groups. We detected no protein band from the cell lysates of the macrophages that showed no expression of ChAT in the previous report (Fujii et al 2017), supporting the reaction speci city of ChAT antibody. Immuno uorescence analysis showed that in animals given hVNS, the number of ChAT-positive cells were slightly higher in the ipsilateral side (left DMV) than the contralateral side (right DMV), yet failing to show statistical difference.…”

Section: Hvns Downregulates Hepatic Expression Of In Ammatory Cytokinsupporting

confidence: 88%

Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

Namgung

2020

Preprint

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Background: Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods: An animal model of hepatitis was generated by intraperitoneal injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN was selectively eliminated by treating animals with capsaicin (CAP). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining.Results: TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). hVNS also induced an increase in phospho-STAT3 in the liver macrophages of ConA-injected animals, suggesting the activation of STAT3 transcription factor associated with cholinergic anti-inflammation. Capsaicin (CAP) treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and also induced an increase in apoptotic caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was reduced by CAP administration. Conclusions: Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

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Section: Hvns Downregulates Hepatic Expression Of In Ammatory Cytokinsupporting

confidence: 88%

Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

Namgung

2020

Preprint

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“…Both corticotropin releasing hormone receptors (CRHRs) and adrenocorticotropic hormone (ACTH) are upregulated in the skin of alopecia areata patients in response to acute emotional stress [87,89,90]. Immune cells, such as T and B cells, DC and macrophages can interact with the nervous system, particularly with the cholinergic system, as they express components such as muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively), choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) [91,92]. In acute stress the upregulation of hormones such as acetylcholine (ACh) can lead to modulation of immune cells functioning as well as upregulation of TNF-α, IFN-γ and IL-6 secretion [91,92], and it can be speculated that in alopecia areata predisposed patients that could result in inflammation and onset of disease.…”

Section: Psychological Stress As Trigger Of Alopecia Areata?mentioning

confidence: 99%

Alopecia areata: A multifactorial autoimmune condition

Simakou

Butcher

Reid

et al. 2019

Journal of Autoimmunity

165

151

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Highlights  Alopecia areata is a polygenic and multifactorial autoimmune disease characterised by non-scarring hair loss.  Autoreactive CD8 + , CD4 + , natural killer cells and plasmacytoid dendritic cells infiltrate around the hair follicles during the growth (anagen) phase.  Increased cytokine activity, particularly IFN-γ, results in disruption of the hair follicle immune privilege and premature termination of the anagen phase, followed by hair follicle atrophy and dystrophy in persistent disease.

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“…α7nAChR is widely expressed on macrophages. In clinical trials, activation of α7nAChR was used to treat inflammatory diseases such as enteritis and rheumatoid arthritis [23], and inhibition of α7nAChR was used to attenuate tissue fibrosis related to inflammation [24]. The regulatory role of α7nAChR in tissue fibrosis and tissue repair has been related to changes in collagen content [25].…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide-induced premature cervical ripening and inflammation in pregnant mice can be alleviated by nicotine

Han¹,

Ding²,

Lin³

et al. 2020

Preprint

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Background Clinical treatment of preterm birth (PTB) is usually dependent on inhibiting uterine contractions. Such therapy is only effective in the short-term and cannot fundamentally low the incidence of PTB. Premature cervical maturation is another important cause of PTB; it is associated with invasion of macrophages, which produce proinflammatory cytokines. We previously found that activation of the alpha-7 nicotinic acetylcholine receptor (α7nAChR) by nicotine alleviates the systemic inflammatory response in murine models of lipopolysaccharide (LPS)-induced PTB, but the underlying mechanisms remain unclear. Methods Cervical tissues were collected from women in preterm and term labor. An animal model of PTB was established by administering 25 µg/kg lipopolysaccharide (LPS) to normal pregnant C57BL/6 mice on gestational day 16 (GD16). PTB animals received 1 mg/kg of α7nAChR agonist nicotine or nicotine combined with 1 µg/kg α7nAChR antagonist α-bungarotoxin (α-BGT) from GD14 to GD17. The gestational age, the rates of preterm birth and the survival rate of pups were recorded. Immunofluorescence staining were utilized for the quantification of α7nAChR expression on cervical macrophages and changes in macrophage polarization, RT-PCR was used to determine the mRNA levels of M1 and M2 macrophage biomarkers. Elisa assay was used to detect changes in fetal inflammation. Immunofluorescence staining and western blotting were used to investigate the signaling pathways underlying nicotine’s promoting LPS-induced conversion of M1 macrophage to M2 in the cervix of PTB animals. Results α7nAChR expression on cervical macrophages and cervical collagen content was decreased in PTB patients and murine models of LPS-induced PTB. The number of M1 cervical macrophages, other pro-inflammatory mediators in the cervix and fetal inflammation was unregulated in pregnant mice following LPS administration. Nicotine treatment reduced the rate of PTB, decreased fetal inflammation, improved maternal and neonatal outcome; nicotine also increased polarization of cervical macrophages toward the anti-inflammatory M2 phenotype possibly by suppressing activation of the MAP kinases JNK and ERK1/2 and nuclear translocation of NF-κB and rescuing the inhibited JAK2/STAT3 and PI3K/AKT pathways. The effects of nicotine were reversed by the selective α7nAChR antagonist α-bungarotoxin (α-BGT). Conclusions Our findings indicate that nicotine prevents LPS-induced cervical ripening and inflammatory response by inducing M2 macrophage polarization, and nicotine may serve as potential anti-premature cervical maturation agents for treatment of PTB.

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Physiological functions of the cholinergic system in immune cells

Cited by 157 publications

References 192 publications

Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

Alopecia areata: A multifactorial autoimmune condition

Lipopolysaccharide-induced premature cervical ripening and inflammation in pregnant mice can be alleviated by nicotine

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