Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction
| Autor: | Dhawan, S., Hiemstra, I. H., Verseijden, C., Hilbers, F. W., te Velde, A. A., Willemsen, L. E.M., Stap, J., den Haan, J. M., de Jonge, W. J., Sub Immunopharmacology, Pharmacology |
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| Přispěvatelé: | Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, CCA -Cancer Center Amsterdam, Cell Biology and Histology, Sub Immunopharmacology, Pharmacology, Molecular cell biology and Immunology, CCA - Immuno-pathogenesis |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Cell Survival Physiology Tight junction proteins Interleukin-1beta Biology Cell Line Tight Junctions Mice Epithelial permeability Occludin Internal medicine Taverne Muscarinic acetylcholine receptor Muscarinic acetylcholine receptor M5 medicine Animals Humans Receptors Cholinergic Interleukin-1 beta Muscarinic acetylcholine receptor M3 Epithelial Cells Muscarinic acetylcholine receptor M2 Muscarinic acetylcholine receptor M1 Myosin light chain Receptors Muscarinic Cell biology Nicotinic agonist Endocrinology Gene Expression Regulation Cholinergic receptors Zonula Occludens-1 Protein Cytokines Cholinergic Acetylcholine medicine.drug |
| Zdroj: | Acta Physiologica, 213(4), 846. Wiley-Blackwell Acta physiologica (Oxford, England), 213(4), 846-859. Wiley-Blackwell Dhawan, S, Hiemstra, I H, Verseijden, C, Hilbers, F W, te Velde, AA, Willemsen, L E M, Stap, J, den Haan, J M M & de Jonge, W J 2015, ' Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction ', Acta Physiologica, vol. 213, no. 4, pp. 846-859 . https://doi.org/10.1111/apha.12469 Acta Physiologica, 213(4), 846-859. Wiley-Blackwell |
| ISSN: | 1748-1708 |
| DOI: | 10.1111/apha.12469 |
| Popis: | Aim Various types of cholinergic receptors are expressed on intestinal epithelia. Their function is not completely understood. We hypothesize that cholinergic receptor activation on epithelium may serve a protective function in cytokine-induced barrier dysfunction. Methods The effect of cholinergic receptor activation on cellular barrier function in epithelial cells was assessed by measuring electrical impedance, and by determining para-cellular transport in transwell experiments. Cell lysates treated with cytokine and/or cholinergic agonists were analysed for cyto- and chemokine production, and tight junction (TJ) protein rearrangement was assessed. Primary colonic epithelial cells were isolated from surgically resected colon tissue of patients with inflammatory bowel disease. Results IL-1β induced production of chemokines (CXCL-1, CXCL-10, IL-8, CCL-7) and led to a rearrangement of TJ proteins (occludin and ZO-1). This response was inhibited by pre-treatment with muscarinic, rather than nicotinic, acetylcholine receptor agonists. Treatment with IL-1β enhanced paracellular permeability (4kD dextran) and reduced impedance across the monolayer, which was counteracted by pre-incubation with acetylcholine, or muscarinic receptor agonist bethanechol. The protective effect of acetylcholine was antagonized by atropine, underscoring muscarinic receptor involvement. IL-1β induced transcription of myosin light chain kinase and phosphorylation of myosin light chain, and this cytokine-induced phosphorylation of MLC was inhibited by muscarinic receptor agonists. Furthermore, in epithelial cells from resection material of patients with Crohn's disease and ulcerative colitis, high expression of CXCL-8 was associated with a reduced choline acetyl transferase expression, suggesting an aberrant epithelial production of ACh in inflammatory context. Conclusion Acetylcholine acts on muscarinic receptors on epithelial cells to maintain epithelial barrier function under inflammatory conditions. |
| Databáze: | OpenAIRE |
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