ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2018
Stimulation of nAchRα7 Receptor Inhibits TNF Synthesis and Secretion in Response to LPS Treatment of Mast Cells by Targeting ERK1/2 and TACE Activation.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review.Journal of neuroinflammation · 2020Pooled it
- Neuroplasticity and neuroimmune interactions with type 2 inflammation in asthma.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- An Autocrine Regulator Loop Involving Tumor Necrosis Factor and Chemokine (C-C motif) Ligand-2 Is Activated by Transforming Growth Factor-β in Rat Basophilic Leukemia-2H3 Mast Cells.International journal of molecular sciences · 2025Article
- Long COVID - a critical disruption of cholinergic neurotransmission?Bioelectronic medicine · 2025Review
- Acetylcholine in the gingival epithelium drives the pathogenesis of periodontitis.Frontiers in cell and developmental biology · 2025Article
- The Polypharmacological Effects of Cannabidiol.Molecules (Basel, Switzerland) · 2023Review
- Review
- [Research advances on the cholinergic inflammatory reflex and inflammation resolution].Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns · 2021Review
- Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles.Frontiers in immunology · 2021Review
- Review
- GTS-21, an α7nAChR agonist, suppressed the production of key inflammatory mediators by PBMCs that are elevated in COPD patients and associated with impaired lung function.Immunobiology · 2020Article
- Mutant Huntingtin affects toll-like receptor 4 intracellular trafficking and cytokine production in mast cells.Journal of neuroinflammation · 2020Article
- Does Cholinergic Stimulation Affect the P2X7 Receptor-Mediated Dye Uptake in Mast Cells and Macrophages?Frontiers in cellular neuroscience · 2020Article
- The synergistic effect of propofol and ulinastatin suppressed the viability of the human lung adenocarcinoma epithelial A549 cell line.Oncology letters · 2018Article
- Activation of the cholinergic anti-inflammatory pathway by GTS-21 attenuates cisplatin-induced acute kidney injury in mice.PloS one · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The cholinergic anti-inflammatory pathway is recognized as one of the main mechanisms of neuromodulation of the immune system. Activation of the α7 nicotinic acetylcholine receptor (nAchRα7) suppresses cytokine synthesis in distinct immune cells but the molecular mechanisms behind this effect remain to be fully described. Mast cells (MCs) are essential players of allergic reactions and innate immunity responses related to chronic inflammation. Activation of TLR4 receptor in MCs leads to the rapid secretion of pre-synthesized TNF from intracellular pools and to the activation of NFκB, necessary for de novo synthesis of TNF and other cytokines. Here we report that the nAchRα7 receptor specific agonist GTS-21 inhibits TLR4-induced secretion of preformed TNF from MCs in vivo and in vitro. Utilizing bone marrow-derived mast cells (BMMCs) it was found that GTS-21 also diminished secretion of de novo synthesized TNF, TNF mRNA accumulation and IKK-dependent p65-NFκB phosphorylation in response to LPS. nAchRα7 triggering prevented TLR4-induced ERK1/2 phosphorylation, which resulted an essential step for TNF secretion due to the phosphorylation of the metallopeptidase responsible for TNF maturation (TACE). Main inhibitory actions of GTS-21 were prevented by AG490, an inhibitor of JAK-2 kinase. Our results show for the first time, that besides the prevention of NFκB-dependent transcription, inhibitory actions of nAchRα7 triggering include the blockade of pathways leading to exocytosis of granule-stored cytokines in MCs.
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