Outcomes of nicotinic modulation on markers of intestinal IgA antibody response

Carrizales‑Luna,Jorge Emmanuel; Reséndiz‑Albor,Aldo Arturo; Arciniega‑Martínez,Ivonne Maciel; Gómez‑López,Modesto; Campos‑Rodríguez,Rafael; Pacheco‑Yépez,Judith; Drago‑Serrano,Maria Elisa

doi:10.3892/br.2022.1595

Outcomes of nicotinic modulation on markers of intestinal IgA antibody response

Authors:
- Jorge Emmanuel Carrizales‑Luna
- Aldo Arturo Reséndiz‑Albor
- Ivonne Maciel Arciniega‑Martínez
- Modesto Gómez‑López
- Rafael Campos‑Rodríguez
- Judith Pacheco‑Yépez
- Maria Elisa Drago‑Serrano
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Affiliations: Laboratory of Biochemistry, Superior School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico, Laboratory of Mucosal Immunology, Superior School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico, Laboratory of Immunonutrition, Postgraduate Studies and Research Section, Superior School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico, Laboratory of Biochemistry, Superior School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico, Department of Biological Systems, Metropolitan Autonomous University, Mexico City 04960, Mexico
Published online on: December 12, 2022 https://doi.org/10.3892/br.2022.1595
Article Number: 13
Copyright: © Carrizales‑Luna et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acetylcholine (ACh), as a ligand of nicotinic acetylcholine receptors (nAChRs), plays a key role in the cholinergic anti‑inflammatory pathway; however, its role in the immunoglobulin A (IgA) response remains unknown. Therefore, the present study aimed to investigate the role of ACh in the intestinal biomarkers involved in IgA synthesis and the polymeric immunoglobulin receptor (pIgR) involved in IgA transcytosis. Groups of mice were administered GTS‑21 (an α7nAChR agonist) or mecamylamine (a non‑selective nAChR antagonist) intraperitoneally for 7 days. Intestinal fluids were used for antibody concentration assessment by ELISA, cell suspensions from Peyer's patches and the lamina propria were obtained for flow cytometric analysis of plasma cells, and CD4⁺ T‑cells expressing intracellular transforming growth factor (TGF)‑β and IgA‑producing interleukin (IL)‑4, ‑5, ‑6 and ‑10, and isolated epithelial cells to determine the levels of pIgR mRNA using reverse transcription‑quantitative PCR. Regarding to the untreated control group, the concentration of IgA was reduced in the mecamylamine group and unaltered in the GTS‑21 group while IgM levels exhibited no differences; the percentage of IgA⁺ plasma cells from Peyer's patches and the lamina propria, and the percentage of TGF‑β⁺/CD4⁺ T‑cells from Peyer's patches were greater in the GTS‑21‑group. In both treatment groups, the percentages of IgM⁺ plasma cells and IL‑6⁺/IL‑10⁺ CD4⁺ T cells were greater in both compartments; pIgR mRNA expression levels decreased in epithelial cells. The percentage of IL‑4 CD4⁺ T‑cells were greater in Peyer's patches and lower in the lamina propria in the mecamylamine group, and the percentage of IL‑5 CD4⁺ T‑cells in the lamina propria were decreased in both treatment groups. These findings require further examination to address the impact of cholinergic modulation on IgA‑transcytosis via pIgR. The present study may be an experimental reference for clinical trials that address the role of nicotinic system in intestinal dysfunctions as postoperative ileus.

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1	Beckmann J and Lips KS: The non-neuronal cholinergic system in health and disease. Pharmacology. 92:286–302. 2013.PubMed/NCBI View Article : Google Scholar
2	Halder N and Lal G: Cholinergic system and its therapeutic importance in inflammation and autoimmunity. Front Immunol. 12(660342)2021.PubMed/NCBI View Article : Google Scholar
3	Felder C: Acetylcholine multiple receptors: Signal transduction through multiple effectors. Faseb J. 9:619–625. 1995.PubMed/NCBI
4	Goverse G, Stakenborg M and Matteoli G: The intestinal cholinergic anti-inflammatory pathway. J Physiol. 594:5771–5780. 2016.PubMed/NCBI View Article : Google Scholar
5	Li Y, Jin L and Chen T: The effects of secretory IgA in the mucosal immune system. Biomed Res Int. 2020(2032057)2020.PubMed/NCBI View Article : Google Scholar
6	Wells JM, Brummer RJ, Derrien M, MacDonald TT, Troost F, Cani PD, Theodorou V, Dekker J, Méheust A, de Vos WM, et al: Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol. 312:G171–G193. 2017.PubMed/NCBI View Article : Google Scholar
7	Schmidt LD, Xie Y, Lyte M, Vulchanova L and Brown DR: Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa. J Neuroimmunol. 185:20–28. 2007.PubMed/NCBI View Article : Google Scholar
8	Wilson ID, Soltis RD, Olson RE and Erlandsen SL: Cholinergic stimulation of immunoglobulin A secretion in rat intestine. Gastroenterology. 83:881–888. 1982.PubMed/NCBI
9	McLoughlin GA, Bradley J, Chapman DM, Temple JG, Hede JE and McFarland J: IgA deficiency and severe post-vagotomy diarrhoea. Lancet. 24:168–170. 1976.PubMed/NCBI View Article : Google Scholar
10	McLoughlin GA, Hede JE, Temple JG, Bradley J, Chapman DM and McFarland J: The role of IgA in the prevention of bacterial colonization of the jejunum in the vagotomized subject. Br J Surg. 6:435–437. 1978.PubMed/NCBI View Article : Google Scholar
11	Arciniega-Martínez IM, Drago-Serrano ME, Salas-Pimentel M, Ventura-Juárez J, Reséndiz-Albor AA and Campos-Rodríguez R: Anterior subdiaphragmatic vagotomy decreases the IgA antibody response in the small intestines of BALB/c mice. J Neuroimmunol. 337(577072)2019.PubMed/NCBI View Article : Google Scholar
12	Pérez-López JA, Rojas-Hernández S, Campos-Rodríguez R, Arciniega-Martínez IM, Cruz-Hernández TR, Reséndiz-Albor AA and Drago-Serrano ME: Posterior subdiaphragmatic vagotomy downmodulates the IgA levels in the small intestine of BALB/c mice. Neuroimmunomodulation. 26:292–300. 2019.PubMed/NCBI View Article : Google Scholar
13	Gottwald T, Lhoták Š and Stead RH: Effect of truncal vagotomy and capsaicin on mast cells and IgA-positive plasma cells in rat jejunal mucosa. Neurogastroenterol Motil. 9:25–32. 1997.PubMed/NCBI View Article : Google Scholar
14	Kilkenny C, Browne WJ, Cuthill IC, Emerson M and Altman DG: Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. Osteoarthr Cartil. 20:256–260. 2012.PubMed/NCBI View Article : Google Scholar
15	Sitapara RA, Gauthier AG, Valdés-Ferrer SI, Lin M, Patel V, Wang M, Martino AT, Perron JC, Ashby CR Jr, Tracey KJ, et al: The α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation. Mol Med. 26(63)2020.PubMed/NCBI View Article : Google Scholar
16	Mina-Osorio P, Rosas-Ballina M, Valdes-Ferrer SI, Al-Abed Y, Tracey KJ and Diamond B: Neural signaling in the spleen controls B-cell responses to blood-borne antigen. Mol Med. 18:618–627. 2012.PubMed/NCBI View Article : Google Scholar
17	Reséndiz-Albor AA, Esquivel R, López-Revilla R, Verdín L and Moreno-Fierros L: Striking phenotypic and functional differences in lamina propria lymphocytes from the large and small intestine of mice. Life Sci. 76:2783–2803. 2005.PubMed/NCBI View Article : Google Scholar
18	Reséndiz-Albor AA, Reina-Garfias H, Rojas-Hernández S, Jarillo-Luna A, Rivera-Aguilar V, Miliar-García A and Campos-Rodríguez R: Regionalization of pIgR expression in the mucosa of mouse small intestine. Immunol Lett. 128:59–67. 2010.PubMed/NCBI View Article : Google Scholar
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
20	Cerutti A: The regulation of IgA class switching. Nat Rev Immunol. 8:421–434. 2008.PubMed/NCBI View Article : Google Scholar
21	Wei H and Wang JY: Role of polymeric immunoglobulin receptor in IgA and IgM transcytosis. Int J Mol Sci. 22:1–20. 2021.PubMed/NCBI View Article : Google Scholar
22	Schmidt PT, Eriksen L, Loftager M, Rasmussen TN and Holst JJ: Fast acting nervous regulation of immunoglobulin A secretion from isolated perfused porcine ileum. Gut. 45:679–685. 1999.PubMed/NCBI View Article : Google Scholar
23	Freier S, Eran M and Faber J: Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine. Gastroenterology. 93:1242–1246. 1987.PubMed/NCBI View Article : Google Scholar
24	Johansen FE and Kaetzel CS: Regulation of the polymeric immunoglobulin receptor and IgA transport: New advances in environmental factors that stimulate pIgR expression and its role in mucosal immunity. Mucosal Immunol. 4:598–602. 2011.PubMed/NCBI View Article : Google Scholar
25	de Jonge WJ and Ulloa L: The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol. 151:915–929. 2007.PubMed/NCBI View Article : Google Scholar
26	Lambrichts DPV, Boersema GSA, Tas B, Wu Z, Vrijland WW, Kleinrensink GJ, Jeekel J, Lange JF and Menon AG: Nicotine chewing gum for the prevention of postoperative ileus after colorectal surgery: A multicenter, double-blind, randomised, controlled pilot study: Int J Colorectal. Dis. 32:1267–1275. 2017.PubMed/NCBI View Article : Google Scholar