The role of TRPA1 ion channels in inflammatory bowel disease
DOI:
https://doi.org/10.33910/2687-1270-2022-3-4-420-431Keywords:
TRP channels, TRPA1, TRPV1, inflammatory bowel disease, ulcerative colitis, Crohn's disease, inflammationAbstract
Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal disorders with complex etiology and pathogenesis. These diseases are marked by a wide range of symptoms, which almost always include inflammatory and pain syndromes. The role of transient receptor potential (TRP) channels channels in gastrointestinal tract illnesses is becoming increasingly better understood. It is suggested that the activity of ankyrin (TRPA1) and vanilloid (TRPV1) ion channels, which are predominantly expressed on capsaicin-sensitive neurons, potentially plays a role in the development of hyperalgesia and neurogenic inflammation. The polymodal nociceptors TRPV1 and TRPA1 are crucial for normal functioning of the gut and its defense mechanisms. The TRPA1 receptor is expressed by immune cells, intestinal epithelial cells involved in inflammatory reactions, and internal sensory neurons of the enteric nervous system (ENS) of the colon. It has been shown that the TRPA1 receptor is activated by a range of endogenous pro-inflammatory molecules. Thus, this receptor is a crucial regulatory structure in inflammation and both acute and chronic pain. However, the contribution of TRPA1 receptors to visceral hypersensitivity and their function in neuroimmune interactions in IBD remains unclear at the moment. This review aims to raise awareness about this issue.
References
Agrawal, M., Allin, K. H., Petralia, F. et al. (2022) Multiomics to elucidate inflammatory bowel disease risk factors and pathways. Nature Reviews. Gastroenterology & Hepatology, vol. 19, no. 6, pp. 399–409. https://doi.org/10.1038/s41575-022-00593-y (In English)
Alaimo, A., Rubert, J. (2019) The pivotal role of TRP channels in homeostasis and diseases throughout the gastrointestinal tract. International Journal of Molecular Sciences, vol. 20, no. 21, article 5277. https://doi.org/10.3390/ijms20215277 (In English)
Angelini, C., Varano, B., Puddu, P. et al. (2017) Direct and intestinal epithelial cell-mediated effects of TLR8 triggering on human dendritic cells, CD14+CD16+ monocytes and γδ T lymphocytes. Frontiers in Immunology, vol. 8, article 1813. https://doi.org/10.3389/fimmu.2017.01813 (In English)
Atreya, R., Bloom, S., Scaldaferri, F. et al. (2016) Clinical effects of a topically applied Toll-like receptor 9 agonist in active moderate-to-severe ulcerative colitis. Journal of Crohn’s and Colitis, vol. 10, no. 11, pp. 1294–1302. https://doi.org/10.1093/ecco-jcc/jjw103 (In English)
Bamps, D., Vriens, J., de Hoon, J. et al. (2020) TRP channel cooperation for nociception: Therapeutic opportunities. Annual Review of Pharmacology and Toxicology, vol. 61, pp. 655–677. https://doi.org/10.1146/annurev-pharmtox-010919-023238 (In English)
Bertin, S., Aoki-Nonaka, Y., Lee, J. et al. (2017) The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1. Gut, vol. 66, no. 9, pp. 1584–1596. https://doi.org/10.1136/gutjnl-2015-310710 (In English)
BioRender (2022). [Online]. Available at: https://biorender.com/ (accessed 17.03.2022). (In English)
Camilleri, M. (2019) Leaky gut: Mechanisms, measurement and clinical implications in humans. Gut, vol. 68, no. 8, pp. 1516–1526. https://doi.org/10.1136/gutjnl-2019-318427 (In English)
Catalan-Serra, I., Sandvik, A. K., Bruland, T. et al. (2017) Gammadelta T Cells in Crohn’s disease: A new player in the disease pathogenesis? Journal of Crohn’s and Colitis, vol. 11, no. 9, pp. 1135–1145. https://doi.org/10.1093/ecco-jcc/jjx039 (In English)
Cattaruzza, F., Johnson, C., Leggit, A. et al. (2013) Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice. American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 304, no. 11, pp. G1002–G1012. https://doi.org/10.1152/ajpgi.00005.2013 (In English)
Chassaing, B., Ley, R. E., Gewirtz, A. T. (2014) Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology, vol. 147, no. 6, pp. 1363–1377. https://doi.org/10.1053/j.gastro.2014.08.033 (In English)
Chubanov, V., Mittermeier, L., Gudermann, T. (2018) Role of kinase-coupled TRP channels in mineral homeostasis. Pharmacology & Therapeutics, vol. 184, pp. 159–176. https://doi.org/10.1016/j.pharmthera.2017.11.003 (In English)
Csekő, K., Beckers, B., Keszthelyi, D., Helyes, Z. (2019) Role of TRPV1 and TRPA1 ion channels in inflammatory bowel diseases: Potential therapeutic targets? Pharmaceuticals, vol. 12, no. 2, article 48. https://doi.org/10.3390/ph12020048 (In English)
D’Aldebert, E., Cenac, N., Rousset, P. et al. (2011) Transient receptor potential vanilloid 4 activated inflammatory signals by intestinal epithelial cells and colitis in mice. Gastroenterology, vol. 140, no. 1, pp. 275–285. https://doi.org/10.1053/j.gastro.2010.09.045 (In English)
De Souza, H. S., Fiocchi, C. (2016) Immunopathogenesis of IBD: Current state of the art. Nature Reviews. Gastroenterology & Hepatology, vol. 13, no. 1, pp. 13–27. https://doi.org/10.1038/nrgastro.2015.186 (In English)
Engel, M. A., Khalil, M., Mueller-Tribbensee, S. M. et al. (2012) The proximodistal aggravation of colitis depends on substance P released from TRPV1-expressing sensory neurons. Journal of Gastroenterology, vol. 47, no. 3, pp. 256–265. https://doi.org/10.1007/s00535-011-0495-6 (In English)
Fichna, J., Mokrowiecka, A., Cygankiewicz, A. I., et al. (2012) Transient receptor potential vanilloid 4 blockade protects against experimental colitis in mice: A new strategy for inflammatory bowel diseases treatment? Neurogastroenterology and Motility, vol. 24, no. 11, pp. e557–e560. https://doi.org/10.1111/j.1365-2982.2012.01999.x (In English)
Flynn, S., Eisenstein, S. (2019) Inflammatory bowel disease presentation and diagnosis. The Surgical Clinics of North America, vol. 99, no. 6, pp. 1051–1062. https://doi.org/10.1016/j.suc.2019.08.001 (In English)
Guan, Q. (2019) A comprehensive review and update on the pathogenesis of inflammatory bowel disease. Journal of Immunology Research, vol. 2019, article 7247238. https://doi.org/10.1155/2019/7247238 (In English)
Hiraishi, K., Kurahara, L.-H., Sumiyoshi, M. et al. (2018) Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel. World Journal of Gastroenterology, vol. 24, no. 35, pp. 4036–4053. https://doi.org/10.3748/wjg.v24.i35.4036 (In English)
Hollander, D. (2013) Intestinal permeability barrier in Crohn’s disease: The difficulty in shifting the paradigm. Digestive Diseases and Sciences, vol. 58, no. 7, pp. 1827–1829. https://doi.org/10.1007/s10620-013-2721-y (In English)
Hosoya, T., Matsumoto, K., Tashima, K. et al. (2014) TRPM8 has a key role in experimental colitis-induced visceral hyperalgesia in mice. Neurogastroenterology and Motility, vol. 26, no. 8, pp. 1112–1121. https://doi.org/10.1111/nmo.12368 (In English)
Issa, C. M., Hambly, B. D., Wang, Y. et al. (2014) TRPV2 in the development of experimental colitis. Scandinavian Journal of Immunology, vol. 80, no. 5, pp. 307–312. https://doi.org/10.1111/sji.12206 (In English)
Kamdar, K., Khakpour, S., Chen, J. et al. (2016) Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease. Cell Host & Microbe, vol. 19, no. 1, pp. 21–31. https://doi.org/10.1016/j.chom.2015.12.006 (In English)
Koivisto, A., Jalava, N., Bratty, R., Pertovaara, A. (2018) TRPA1 antagonists for pain relief. Pharmaceuticals, vol. 11, no. 4, article 117. https://doi.org/10.3390/ph11040117 (In English)
Korolkova, O. Y., Myers, J. N., Pellom, S. T. et al. (2015) Characterization of serum cytokine profile in predominantly colonic inflammatory bowel disease to delineate ulcerative and Crohn’s colitides. Clinical Medicine Insights: Gastroenterology, vol. 8, pp. 29–44. https://doi.org/10.4137/CGast.S20612 (In English)
Kun, J., Szitter, I., Kemény, A. et al. (2014) Upregulation of the transient receptor potential ankyrin 1 ion channel in the inflamed human and mouse colon and its protective roles. PloS ONE, vol. 9, no. 9, article e108164. https://doi.org/10.1371/journal.pone.0108164 (In English)
Kurahara, L. H., Hiraishi, K., Hu, Y. et al. (2017) Activation of myofibroblast TRPA1 by steroids and pirfenidone ameliorates fibrosis in experimental Crohn’s disease. Cellular and Molecular Gastroenterology and Hepatology, vol. 5, no. 3, pp. 299–318. https://doi.org/10.1016/j.jcmgh.2017.12.005 (In English)
Landini, L., Souza Monteiro de Araujo, D., Titiz, M. et al. (2022) TRPA1 role in inflammatory disorders: What is known so far? International Journal of Molecular Sciences, vol. 23, no. 9, article 4529. https://doi.org/10.3390/ijms23094529 (In English)
Lu, Y., Li, X., Liu, S. et al. (2018) Toll-like receptors and inflammatory bowel disease. Frontiers in Immunology, vol. 9, article 72. https://doi.org/10.3389/fimmu.2018.00072 (In English)
Matsumoto, K., Yamaba, R., Inoue, K. et al. (2018) Transient receptor potential vanilloid 4 channel regulates vascular endothelial permeability during colonic inflammation in dextran sulphate sodium-induced murine colitis. British Journal of Pharmacology, vol. 175, no. 1, pp. 84–99. https://doi.org/10.1111/bph.14072 (In English)
Meents, J. E., Ciotu, C. I., Fischer, M. (2019) TRPA1: A molecular view. Journal of Neurophysiology, vol. 121, no. 2, pp. 427–443. https://doi.org/10.1152/jn.00524.2018 (In English)
Mirsepasi-Lauridsen, H. C., Vrankx, K., Engberg, J. et al. (2018) Disease-specific enteric microbiome dysbiosis in inflammatory bowel disease. Frontiers in Medicine, vol. 5, article 304. https://doi.org/10.3389/fmed.2018.00304 (In English)
Moossavi, S., Rezaei, N. (2013) Toll-like receptor signalling and their therapeutic targeting in colorectal cancer. International Immunopharmacology, vol. 16, no. 2, pp. 199–209. https://doi.org/10.1016/j.intimp.2013.03.017 (In English)
Moparthi, L., Zygmunt, P. M. (2020) Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel. Cell Calcium, vol. 91, article 102255. https://doi.org/10.1016/j.ceca.2020.102255 (In English)
Morgan, M. E., Koelink, P. J., Zheng, B. et al. (2014) Toll-like receptor 6 stimulation promotes T-helper 1 and 17 responses in gastrointestinal-associated lymphoid tissue and modulates murine experimental colitis. Mucosal Immunology, vol. 7, no. 5, pp. 1266–1277. https://doi.org/10.1038/mi.2014.16 (In English)
Nummenmaa, E., Hämäläinen, M., Pemmari, A. et al. (2020) Transient receptor potential ankyrin 1 (TRPA1)
is involved in upregulating interleukin-6 expression in osteoarthritic chondrocyte models. International Journal of Molecular Sciences, vol. 22, no. 1, article 87. https://doi.org/10.3390/ijms22010087 (In English)
Pazmandi, J., Kalinichenko, A., Ardy, R. C. et al. (2019) Early-onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms. Immunological Reviews, vol. 287, no. 1, pp. 162–185. https://doi.org/10.1111/imr.12726 (In English)
Piovani, D., Danese, S., Peyrin-Biroulet, L. et al. (2019) Environmental risk factors for inflammatory bowel diseases: An umbrella review of meta-analyses. Gastroenterology, vol. 157, no. 3, pp. 647–659. https://doi.org/10.1053/j.gastro.2019.04.016 (In English)
Quraishi, M. N., Shaheen, W., Oo, Y. H., Iqbal, T. H. (2020) Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease. Clinical and Experimental Immunology, vol. 199, no. 1, pp. 24–38. https://doi.org/10.1111/cei.13397 (In English)
Regner, E. H., Ohri, N., Stahly, A. et al. (2018) Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota. Arthritis Research & Therapy, vol. 20, no. 1, article 149. https://doi.org/10.1186/s13075-018-1639-3 (In English)
Roda, G., Chien Ng, S., Kotze, P. G. et al. (2020) Crohn’s disease. Nature Reviews. Disease Primers, vol. 6, no. 1, article 22. https://doi.org/10.1038/s41572-020-0156-2 (In English)
Ruparel, N. B., Patwardhan, A. M., Akopian, A. N. et al. (2011) Desensitization of transient receptor potential ankyrin 1 (TRPA1) by the TRP vanilloid 1-selective cannabinoid arachidonoyl-2 chloroethanolamine. Molecular Pharmacology, vol. 80, no. 1, pp. 117–123. https://doi.org/10.1124/mol.110.068940 (In English)
Sahoo, N., Gu, M., Zhang, X. et al. (2017) Gastric acid secretion from parietal cells is mediated by a Ca2+ efflux channel in the tubulovesicle. Developmental Cell, vol. 41, no. 3, pp. 262–273. https://doi.org/10.1016/j.devcel.2017.04.003 (In English)
Santoni, G., Farfariello, V., Liberati, S. et al. (2013) The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses. Frontiers in Immunology, vol. 4, article 34. https://doi.org/10.3389/fimmu.2013.00034 (In English)
Souza Monteiro de Araujo, D., Nassini, R., Geppetti, P. et al. (2020) TRPA1 as a therapeutic target for nociceptive pain. Expert Opinion on Therapeutic Targets, vol. 24, no. 10, pp. 997–1008. https://doi.org/10.1080/14728222.2020.1815191 (In English)
Sultan, S., El-Mowafy, M., Elgaml, A. et al. (2021) Metabolic influences of gut microbiota dysbiosis on inflammatory bowel disease. Frontiers in Physiology, vol. 12, article 715506. https://doi.org/10.3389/fphys.2021.715506 (In English)
Suo, Y., Wang, Z., Zubcevic, L. et al. (2020) Structural insights into electrophile irritant sensing by the human TRPA1 channel. Neuron, vol. 105, no. 5, pp. 882–894. https://doi.org/10.1016/j.neuron.2019.11.023 (In English)
Talavera, K., Startek, J. B., Alvarez-Collazo, J. et al. (2020) Mammalian transient receptor potential TRPA1 channels: From structure to disease. Physiological Reviews, vol. 100, no. 2, pp. 725–803. https://doi.org/10.1152/physrev.00005.2019 (In English)
Thachil, E., Hugot, J.-P., Arbeille, B. et al. (2012) Abnormal activation of autophagy-induced crinophagy in Paneth cells from patients with Crohn’s disease. Gastroenterology, vol. 142, no. 5, pp. 1097–1099. https://doi.org/10.1053/j.gastro.2012.01.031 (In English)
Uhlig, H. H., Powrie, F. (2018) Translating immunology into therapeutic concepts for inflammatory bowel disease. Annual Review of Immunology, vol. 36, pp. 755–781. https://doi.org/10.1146/annurev-immunol-042617-053055 (In English)
Vijay, K. (2018) Toll-like receptors in immunity and inflammatory diseases: Past, present, and future. International Immunopharmacology, vol. 59, pp. 391–412. https://doi.org/10.1016/j.intimp.2018.03.002 (In English)
Wang, Q., Xu, K.-Q., Qin, X.-R. et al. (2016) Association between physical activity and inflammatory bowel disease risk: A meta-analysis. Digestive and Liver Disease, vol. 48, no. 12, pp. 1425–1431. https://doi.org/10.1016/j.dld.2016.08.129 (In English)
Yamamoto-Furusho, J. K., Parra-Holguín, N. N. (2021) Emerging therapeutic options in inflammatory bowel disease. World Journal of Gastroenterology, vol. 27, no. 48, pp. 8242–8261. https://doi.org/10.3748/wjg.v27.i48.8242 (In English)
Yang, J.-Y., Kim, M.-S., Kim, E. et al. (2016) Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated Interferon-β production. Immunity, vol. 44, no. 4, pp. 889–900. https://doi.org/10.1016/j.immuni.2016.03.009 (In English)
Yue, L., Xu, H. (2021) TRP channels in health and disease at a glance. Journal of Cell Science, vol. 134, no. 13, article jcs258372. https://doi.org/10.1242/jcs.258372 (In English)
Zevallos, V. F., Raker, V., Tenzer, S. et al. (2017) Nutritional wheat amylase-trypsin inhibitors promote intestinal inflammation via activation of myeloid cells. Gastroenterology, vol. 152, no. 5, pp. 1100–1113. https://doi.org/10.1053/j.gastro.2016.12.006 (In English)
Zhu, L., Shi, T., Zhong, C. et al. (2017) IL-10 and IL-10 receptor mutations in very early onset inflammatory bowel disease. Gastroenterology Research, vol. 10, no. 2, pp. 65–69. https://doi.org/10.14740/gr740w (In English)
Zielińska, M., Jarmuż, A., Wasilewski, A. et al. (2015) Role of transient receptor potential channels in intestinal inflammation and visceral pain: novel targets in inflammatory bowel diseases. Inflammatory Bowel Diseases, vol. 21, no. 2, pp. 419–427. https://doi.org/10.1097/MIB.0000000000000234 (In English)
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