ArticlePloS one2019
GTS-21 has cell-specific anti-inflammatory effects independent of α7 nicotinic acetylcholine receptors.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- CNS-Spleen Axis - a Close Interplay in Mediating Inflammatory Responses in Burn Patients and a Key to Novel Burn Therapeutics.Frontiers in immunology · 2021Pooled it
- Nicotine Suppresses Human Memory Th Cell Subsets With Preferential Effects on Central Memory Th Cells in an α7 Nicotinic Acetylcholine Receptor-Dependent Manner.European journal of immunology · 2026Article
- Alpha-7 nicotinic acetylcholine receptor: targeting the interplay between inflammation, renin-angiotensin aldosterone system, and nervous system for the novel treatment of heart failure.Frontiers in pharmacology · 2026Review
- Effects of Swapping 5HT3 and α7 Residues in Chimeric Receptor Proteins on RIC3 and NACHO Chaperone Actions.Molecules (Basel, Switzerland) · 2025Article
- TFEB-mediated proinflammatory response in murine macrophages induced by acute Alpha7 nicotinic receptor activation.Journal of leukocyte biology · 2025Article
- Elucidating the role of peripheral monocyte nicotinic acetylcholine receptors and inflammation in cognitive outcomes in older adults.Biogerontology · 2025Article
- The Role of α7-Nicotinic Acetylcholine Receptors in the Pathophysiology and Treatment of Parkinson's Disease.International journal of molecular sciences · 2025Review
- Targeting the cholinergic anti-inflammatory pathway: an innovative strategy for treating diseases.Molecular biology reports · 2025Review
- The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic.PloS one · 2025Article
- Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.Inflammation · 2024Article
- GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4International journal of molecular sciences · 2023Article
- Article
- The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 does not affect food intake in rats.Pharmacology, biochemistry, and behavior · 2022Article
- The Alpha 7 Nicotinic Acetylcholine Receptor Does Not Affect Neonatal Brain Injury.Biomedicines · 2022Article
- Medicinal nicotine in COVID-19 acute respiratory distress syndrome, the new corticosteroid.World journal of critical care medicine · 2022Review
- Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications.Biomolecules · 2022Review
- Small-molecule drugs development for Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- Vagal-α7nAChR signaling is required for lung anti-inflammatory responses and arginase 1 expression during an influenza infection.Acta pharmacologica Sinica · 2021Article
- The Positive Allosteric Modulation of alpha7-Nicotinic Cholinergic Receptors by GAT107 Increases Bacterial Lung Clearance in Hyperoxic Mice by Decreasing Oxidative Stress in Macrophages.Antioxidants (Basel, Switzerland) · 2021Article
- Cardioprotective role of GTS-21 by attenuating the TLR4/NF-κB pathway in streptozotocin-induced diabetic cardiomyopathy in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α7 Nicotinic acetylcholine receptors (nAChRs) reportedly reduce inflammation by blocking effects of the important pro-inflammatory transcription factor, nuclear factor kappa-light chain-enhancer of B cells (NFκB). The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation. However, mechanistic details of α7 nAChR involvement in GTS-21 effects on inflammatory pathways remain unclear. Here, we investigate how GTS-21 acts in two cell systems including the non-immune rat pituitary cell line GH4C1 expressing an NFκB-driven reporter gene and cytokine secretion by ex vivo cultures of primary mouse macrophages activated by lipopolysaccharide (LPS). GTS-21 does not change TNF-stimulated NFκB signaling in GH4C1 cells expressing rat α7 nAChRs, suggesting that GTS-21 requires additional unidentified factors besides α7 nAChR expression to allow anti-inflammatory effects in these cells. In contrast, GTS-21 dose-dependently suppresses LPS-induced IL6 and TNF secretion in primary mouse macrophages endogenously expressing α7 nAChRs. GTS-21 also blocks TNF-induced phosphorylation of NFκB inhibitor alpha (IκBα), an important intermediary in NFκB signaling. However, α7 antagonists methyllycaconitine and α-bungarotoxin only partially reverse GTS-21 blockade of IL6 and TNF secretion. Further, GTS-21 significantly inhibited LPS-induced IL6 and TNF secretion in macrophages isolated from knockout mice lacking α7 nAChRs. These data indicate that even though a discrete component of the anti-inflammatory effects of GTS-21 requires expression of α7 nAChRs in macrophages, GTS-21 also has anti-inflammatory effects independent of these receptors depending on the cellular context.
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