Deletion of muscarinic type 1 acetylcholine receptors alters splenic lymphocyte functions and splenic noradrenaline concentration

Hainke, S.; Wildmann, Johannes; Rey, Adriana del

doi:10.1016/j.intimp.2015.05.010

Cited by 9 publications

(3 citation statements)

References 31 publications

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“…In mice and humans, stimulation of β 2 AR activates NOD2 signaling, promotes T cell differentiation, and regulates the secretion of related cytokines and inflammation, according to a study [ 22 ] on dendritic cells. CHRNA7 regulates the function of immune cells in the spleen and is involved in regulating the production of proinflammatory cytokines, which are an integral part of the cholinergic anti-inflammatory pathway that regulates inflammation [ 23 ]. The mechanism by which Salvia miltiorrhiza plays an anti-inflammatory role through the cholinergic anti-inflammatory pathway is not clear.…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Zhu

Zhang

Long

et al. 2021

Computational and Mathematical Methods in Medicine

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Using network pharmacology and molecular docking, this study investigated the molecular mechanisms by which the active components in Salvia miltiorrhiza can alleviate acute pancreatitis. Initially, the active components of Salvia miltiorrhiza and the targets collected from the GeneCards database were screened based on the platform of systematic pharmacology analysis of traditional Chinese medicine. Subsequently, the active components were intersected with the disease targets. Also, interactions among the targets were computed using the STRING database. Biological function and pathway enrichment were analyzed using the Cluster Profiler package in the R software. Protein-protein interaction and component target pathway network were constructed using the Cytoscape software. Ultimately, the key targets and their corresponding components in the network were verified using the AutoDock Vina software. The results showed Salvia miltiorrhiza had 111 targets for acute pancreatitis. The biological process (BP) analysis showed that the active components of Salvia miltiorrhiza induced a drug response, positive regulation of transcription by RNA polymerase II promoter, signal transduction, positive regulation of cell proliferation, and negative regulation of apoptosis. Furthermore, the KEGG enrichment analysis screened 118 ( P < 0.05 ) signaling pathways, such as the pathways related to cancer, neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, and cAMP signaling pathway, to name a few. Finally, molecular docking showed that the active components of Salvia miltiorrhiza had a good binding affinity with their corresponding target proteins. Through network pharmacology, this study predicted the potential pharmacodynamic material basis and the mechanisms by which Salvia miltiorrhiza can treat acute pancreatitis. Moreover, this study provided a scientific basis for mining the pharmacodynamic components of Salvia miltiorrhiza and expanding the scope of its clinical use.

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Section: Discussionmentioning

confidence: 99%

Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Zhu

Zhang

Long

et al. 2021

Computational and Mathematical Methods in Medicine

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“…4) For example, after immunization, M 1 and M 5 mAChR double-deficient mice produce significantly less, while α7 nAChR-deficient mice produce significantly more, total and antigen-specific immunoglobulin G (IgG) 1 and interleukin (IL)-6 than do their wild-type counterparts. 5,6) IgM production, by contrast, is unaffected. This suggests that both mAChRs and nAChRs affect B cell function by regulating IL-6 production, which in turn leads to modulation of antibody class switching from IgM to IgG.…”

Section: Introductionmentioning

confidence: 87%

Muscarinic Acetylcholine Receptors Modulate Interleukin-6 Production and Immunoglobulin Class Switching in Daudi Cells

Mashimo

Fujii

Sakagawa

et al. 2020

Biological & Pharmaceutical Bulletin

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B cells express muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively). Following immunization with ovalbumin, serum immunoglobulin G (IgG) and interleukin (IL)-6 levels were lower in M 1 and M 5 mAChR double-deficient mice and higher in α7 nAChR-deficient mice than in wild-type mice. This suggests mAChRs participate in the cytokine production involved in B cell differentiation into plasma cells, which induces immunoglobulin class switching from IgM to IgG. However, because these results were obtained with conventional knockout mice, in which all cells in the body were affected, the specific roles of these receptors expressed in B cells remains unclear. In the present study, Daudi B lymphoblast cells were used to investigate the specific roles of mAChRs and nAChR in B cells. Stimulating Daudi cells using Pansorbin cells (heat-killed, formalin-fixed Staphylococcus aureus coated with protein A) upregulated expression of M 1-M 4 mAChRs and the α4 nAChR subunit. Under these conditions, mAChRs, but not nAChRs, mediated immunoglobulin class switching to IgG. This effect was blocked by scopolamine, a non-selective mAChR antagonist, and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a G q/11-coupled M 1 , M 3 , M 5 antagonist. In addition, IL-6 secretion was further enhanced following mAChR activation. Thus, G q/11-coupled mAChRs expressed in B cells thus appear to contribute to IL-6 production and B cell maturation into IgG-producing plasma cells.

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“…) mice show increased splenic noradrenaline production and a decrease in the number of IgG-producing B cells (283). M 3 mAChR in B cells show an increase in calcium signaling and c-Fos gene expression, thereby affecting several downstream signaling pathways (284).…”

Section: Role In B Cellsmentioning

confidence: 99%

Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity

2021

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Neurological and immunological signals constitute an extensive regulatory network in our body that maintains physiology and homeostasis. The cholinergic system plays a significant role in neuroimmune communication, transmitting information regarding the peripheral immune status to the central nervous system (CNS) and vice versa. The cholinergic system includes the neurotransmitter\ molecule, acetylcholine (ACh), cholinergic receptors (AChRs), choline acetyltransferase (ChAT) enzyme, and acetylcholinesterase (AChE) enzyme. These molecules are involved in regulating immune response and playing a crucial role in maintaining homeostasis. Most innate and adaptive immune cells respond to neuronal inputs by releasing or expressing these molecules on their surfaces. Dysregulation of this neuroimmune communication may lead to several inflammatory and autoimmune diseases. Several agonists, antagonists, and inhibitors have been developed to target the cholinergic system to control inflammation in different tissues. This review discusses how various molecules of the neuronal and non-neuronal cholinergic system (NNCS) interact with the immune cells. What are the agonists and antagonists that alter the cholinergic system, and how are these molecules modulate inflammation and immunity. Understanding the various functions of pharmacological molecules could help in designing better strategies to control inflammation and autoimmunity.

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Deletion of muscarinic type 1 acetylcholine receptors alters splenic lymphocyte functions and splenic noradrenaline concentration

Cited by 9 publications

References 31 publications

Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Muscarinic Acetylcholine Receptors Modulate Interleukin-6 Production and Immunoglobulin Class Switching in Daudi Cells

Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity

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