The role of the cholinergic anti‐inflammatory pathway in autoimmune rheumatic diseases

Lv, Jiaqi; Ji, Xiaoxiao; Li, Zhen; Hu, Hao

doi:10.1111/sji.13092

Cited by 9 publications

(5 citation statements)

References 128 publications

(298 reference statements)

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“…Cholinergic anti‐inflammatory pathway (CAP) is a newly discovered neuro‐immunomodulatory pathway distinct from the classical humoral anti‐inflammatory signaling [25] . In this vagus nerve‐dependent anti‐inflammatory response, CNS sends certain signals to celiac ganglia via the vagal efferent arm and splanchnic nerve when conferring the risks of excessive inflammation.…”

Section: Resultsmentioning

confidence: 99%

“…Cholinergic anti-inflammatory pathway (CAP) is a newly discovered neuro-immunomodulatory pathway distinct from the classical humoral anti-inflammatory signaling. [25] In this vagus nerve-dependent anti-inflammatory response, CNS sends certain signals to celiac ganglia via the vagal efferent arm and splanchnic nerve when conferring the risks of excessive inflammation. After that, norepinephrine (NE) is released from the splenic nerve, and promotes the production of acetylcholine (Ach) production, which then acts on alpha 7 nicotinic acetylcholine receptor (α7nAChR) expressed by macrophages to initiate the intracellular molecular events.…”

Section: Osthole Exerts Its Anti-inflammatory Activity By Activating ...mentioning

confidence: 99%

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Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses

Li,

Yuan

et al. 2024

Chemistry & Biodiversity

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Osthole (also known as Osthol) is the main anti‐inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality‐controlled component according the Chinese Pharmacopoeia. However, its underlying anti‐inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF‐α, but not IL‐6 in the classical LPS‐stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF‐κB signalling pathways, of which the former was dose‐dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose‐dependently up‐regulated the expression of the key cholinergic anti‐inflammatory pathway regulator α7nAChR, and the TNF‐α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF‐α by promoting the expression of α7nAChR, thereby activate the vagus nerve‐dependent cholinergic anti‐inflammatory pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Osthole Exerts Its Anti-inflammatory Activity By Activating ...mentioning

confidence: 99%

Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses

Li,

Yuan

et al. 2024

Chemistry & Biodiversity

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“…This pathway can modulate the activity of immune cells through activation of nicotinic acetylcholine receptors on macrophages, dendritic cells, monocytes, and T-and B-lymphocytes. Furthermore, it can inhibit cell proliferation and differentiation, as well as suppress cytokine release (22). The exact role of acetylcholinesterase inhibitors and their interaction with the cholinergic pathway and inflammatory reactions in MG has not been established.…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Symptomatic, pharmacological treatment of myasthenia gravis.

Remijn-Nelissen,

Bakker,

Van Gelder

et al. 2023

rrnmf

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Myasthenia gravis (MG) is a chronic antibody-mediated autoimmune disease. The most frequent form is MG with antibodies directed against the acetylcholine receptor on the postsynaptic membrane. The first step in the treatment of autoimmune myasthenia gravis consists of symptomatic therapy. If this is insufficiently effective, the next step is to start immunosuppressive treatment with corticosteroids, usually prednisolone. A corticoid-sparing agent is often added because of the long long-term side effects of high doses of corticosteroids. The position of emerging immunomodulatory therapies targeting B-and T-cells, the complement cascade, the neonatal Fc receptor, and cytokines associated with antibody production in the treatment of MG is currently unclear. However, it is likely that symptomatic treatment will remain the cornerstone in the management of patients with MG in the foreseeable future. In this review, we provide an overview of currently available symptomatic treatments and recent advances in this field. Pyridostigmine, an acetylcholinesterase inhibitor, is the most commonly used symptomatic drug for MG. Acetylcholinesterase inhibitors prolong and enhance the effect of acetylcholine on muscarinic and nicotinic receptors. In addition, there is evidence that pyridostigmine may also have an anti-inflammatory effect. Pyridostigmine is moderately effective, but side effects are frequently reported by patients. Other therapies include amifampridine and sympathomimetics such as ephedrine, salbutamol, and terbutaline. At present, there is insufficient evidence for the use of amifampridine as monotherapy or as add-on therapy to pyridostigmine. The addition of β2-adrenergic agonists to pyridostigmine may possibly be beneficial in some patients, however, well-designed randomized trials are needed to establish their efficacy. Emerging symptomatic therapies include ClC-channel blockers, fast-skeletal muscle troponin activators, and antisense oligodeoxynucleotides. These therapies appear to be promising, with fewer side effects than pyridostigmine. However, phase III clinical trials are needed to assess their effectiveness and determine their place in symptomatic treatment of MG patients.

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“…It is thought that the anti-inflammatory effects of smoking are caused by nicotine's activation of the cholinergic anti-inflammatory pathway. The cholinergic anti-inflammatory pathway, which is implicated in interactions between the autonomic nervous system and the immune system, may also play a role in autoimmune arthritis by regulating cytokine levels and the activities of immune cells [12]. Alpha7 nicotinic acetylcholine receptor (α7 nAChR), expressed in a variety of immune cells, including TH17 cells, is a component of cholinergic pathways; it not only inhibits the release of cytokines but also regulates the activity of immune cells [12].…”

Section: Introductionmentioning

confidence: 99%

“…The cholinergic anti-inflammatory pathway, which is implicated in interactions between the autonomic nervous system and the immune system, may also play a role in autoimmune arthritis by regulating cytokine levels and the activities of immune cells [12]. Alpha7 nicotinic acetylcholine receptor (α7 nAChR), expressed in a variety of immune cells, including TH17 cells, is a component of cholinergic pathways; it not only inhibits the release of cytokines but also regulates the activity of immune cells [12]. Treatment of fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients with agonists of α7 nAChR reduced the levels of the pro-inflammatory cytokines IL-6 and IL-8 [13].…”

Section: Introductionmentioning

confidence: 99%

The Expression of the Alpha7 Nicotinic Acetylcholine Receptor and the Effect of Smoking in Curdlan-Administered SKG Mice

Kim,

Lee,

Lee

et al. 2023

Biomedicines

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Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR+ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR+ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR+ and IL-17A+ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR+IL-17A+ and α7 nAChR+IL-17A+FOXP3+ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR+ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR+ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice.

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The role of the cholinergic anti‐inflammatory pathway in autoimmune rheumatic diseases

Cited by 9 publications

References 128 publications

Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses

Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses

Symptomatic, pharmacological treatment of myasthenia gravis.

The Expression of the Alpha7 Nicotinic Acetylcholine Receptor and the Effect of Smoking in Curdlan-Administered SKG Mice

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