The role of α7nAChR in controlling the anti-inflammatory/anti-arthritic action of galantamine
| Autor: | Rowaida Refaat, Mennatallah A. Gowayed, Hanan S. El-Abhar, Ahmed S. Attia, Kathrin Rothe, Ulf Wagner, Christoph Baerwald, Manuela Rossol |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male alpha7 Nicotinic Acetylcholine Receptor Anti-Inflammatory Agents Spleen Inflammation Nicotinic Antagonists Pharmacology Biochemistry Peripheral blood mononuclear cell T-Lymphocytes Regulatory Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Immune system Galantamine medicine Animals Humans business.industry medicine.disease Arthritis Experimental Rats 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Rheumatoid arthritis Antirheumatic Agents Cholinergic Tumor necrosis factor alpha Cholinesterase Inhibitors medicine.symptom business medicine.drug |
| Zdroj: | Biochemical pharmacology. 170 |
| ISSN: | 1873-2968 |
| Popis: | Objective The evolution of the “cholinergic anti-inflammatory pathway” and the fact that the α 7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is present in the spleen, joint and on the surface of lymphocytes, opened up the prospective in this study of targeting the α7nAChR by the anticholinesterase and cholinergic drug, galantamine, to control inflammation in rheumatoid arthritis (RA). Methods Twelve-adjuvant arthritic rats were exposed to the selective α7nAChR blocker methylcaconitine citrate 15 min before galantamine treatment. As control, six adjuvant arthritic rats were treated with galantamine and six others were untreated. After five days TNF-α levels were assessed in spleen and joints, while reduced glutathione was measured in blood and joint tissue. In the second part, magnetically sorted CD4 + T cells from peripheral blood mononuclear cells of RA patients and healthy donors were used to sort CD4 + CD25 – primary T cells (Tresp) and CD4 + CD25 + CD127low Tregs. The suppressive function of Tregs was investigated after incubation with galantamine using flow cytometry. Cell culture supernatants were analyzed for TNF-α and IL-10 levels after three days incubation period of Tregs with Tresp. The effect of galantamine on Tregs was then blocked by α-Bungarotoxin and the same assay has been repeated. Results & conclusion Selective α7nAChR blockade interrupted the anti-inflammatory effect of galantamine in the spleen and joints of arthritic rats. In healthy donors, galantamine could strengthen the suppressive activity of Tregs; while in RA patients it did not modulate the function of Tregs significantly. Further studies are necessary to investigate whether modulation of the cholinergic nervous system, especially α7nAChR, could have impact on the disturbed immune system in RA, which may open up a new treatment option of autoimmune diseases. |
| Databáze: | OpenAIRE |
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