https://doi.org/10.4081/ejh.2022.3415
Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway
Submitted: 4 April 2022
Accepted: 16 May 2022
Published: 23 May 2022
Accepted: 16 May 2022
Abstract Views: 1116
PDF: 792
HTML: 39
HTML: 39
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Recent evidence suggests that endoplasmic reticulum (ER) stress plays a vital role in inflammatory bowel disease (IBD). Therefore, the aim of this study was to investigate the mechanism by which ER stress promotes inflammatory response in IBD. The expression of Gro-α, IL-8 and ER stress indicator Grp78 in colon tissues from patients with Crohn’s disease (CD) and colonic carcinoma was analyzed by immunohistochemistry staining. Colitis mouse model was established by the induction of trinitrobenzene sulphonic acid (TNBS), and the mice were treated with ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Then the body weight, colon length and colon inflammation were evaluated, and Grp78 and Gro-α in colon tissues were detected by immunohistochemistry. Epithelial cells of colon cancer HCT116 cells were treated with tunicamycin to induce ER stress. Grp78 was detected by Western blot, and chemokines were measured by PCR and ELISA. The expression levels of Grp78, Gro-α and IL-8 were significantly upregulated in intestinal tissues of CD patients. Mice with TNBS induced colitis had increased expression of Grp78 and Gro-α in colonic epithelia. TUDCA reduced the severity of TNBS-induced colitis. In HCT116 cells, tunicamycin increased the expression of Grp78, Gro-α and IL-8 in a concentration-dependent manner. Furthermore, p38 MAPK inhibitor significantly inhibited the upregulation of Gro-α and IL-8 induced by tunicamycin. In conclusion, ER stress promotes inflammatory response in IBD, and the effects may be mediated by the activation of p38 MAPK signaling pathway.
Kaser A, Zeissig S, Blumberg R S. Inflammatory bowel disease. Annu Rev Immunol 2010;28:573-621.
DOI: https://doi.org/10.1146/annurev-immunol-030409-101225
Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015;12:205-27.
DOI: https://doi.org/10.1038/nrgastro.2015.34
De Souza HSP, Fiocchi C, Iliopoulos D3 The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 2017;14:739-49.
DOI: https://doi.org/10.1038/nrgastro.2017.110
Cao SS. Endoplasmic reticulum stress and unfolded protein response in inflammatory bowel disease. Inflamm Bowel Dis 2015;21:636-44.
DOI: https://doi.org/10.1097/MIB.0000000000000238
Ma X, Dai Z, Sun K, Zhang Y, Chen J, Yang Y, et al. Intestinal epithelial cell endoplasmic reticulum stress and inflammatory bowel disease pathogenesis: An update review. Front Immunol 2017;8:1271.
DOI: https://doi.org/10.3389/fimmu.2017.01271
Cao SS. Epithelial ER stress in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2016;22:984-93.
DOI: https://doi.org/10.1097/MIB.0000000000000660
Luo K, Cao SS. Endoplasmic reticulum stress in intestinal epithelial cell function and inflammatory bowel disease. Gastroenterol Res Pract 2015;2015:328791.
DOI: https://doi.org/10.1155/2015/328791
Kulkarni N, Pathak M, Lal G. Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance. J Leukoc Biol 2017;101:377-94.
DOI: https://doi.org/10.1189/jlb.1RU0716-327R
Wu M, Sun M, Lai Q, Lu Y, Fu Y, Peng Y, et al. Chemokine ligand 13 expression is abundant in the tumor microenvironment and indicates poor prognosis of kidney clear cell carcinoma. Biocell 2021;45:589–97.
DOI: https://doi.org/10.32604/biocell.2021.013882
Danese S, Gasbarrini A. Chemokines in inflammatory bowel disease. J Clin Pathol 2005;58:1025-7.
DOI: https://doi.org/10.1136/jcp.2005.030916
Uguccioni M, Gionchetti P, Robbiani DF, Rizzello F, Peruzzo S, Campieri M, et al. Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis. Am J Pathol 1999;155:331-6.
DOI: https://doi.org/10.1016/S0002-9440(10)65128-0
Katsuta T, Lim C, Shimoda K, Shibuta K, Mitra P, Banner BF, et al. Interleukin-8 and SDF1-alpha mRNA expression in colonic biopsies from patients with inflammatory bowel disease. Am J Gastroenterol 2000;95:3157-64.
DOI: https://doi.org/10.1111/j.1572-0241.2000.03289.x
Ina K, Kusugami K, Yamaguchi T, Imada A, Hosokawa T, Ohsuga M, et al. Mucosal interleukin-8 is involved in neutrophil migration and binding to extracellular matrix in inflammatory bowel disease. Am J Gastroenterol 1997;92:1342-6.
Mahida YR, Ceska M, Effenberger F, Kurlak L, Lindley I and Hawkey CJ. Enhanced synthesis of neutrophil-activating peptide-1/interleukin-8 in active ulcerative colitis. Clin Sci (Lond) 1992;82:273-5
DOI: https://doi.org/10.1042/cs0820273
Alzoghaibi MA, Al-Mofleh IA, Al-Jebreen AM. Neutrophil chemokines GCP-2 and GRO-alpha in patients with inflammatory bowel disease. J Dig Dis 2008;9:144-8.
DOI: https://doi.org/10.1111/j.1751-2980.2008.00336.x
Mitsuyama K, Tsuruta O, Tomiyasu N, Takaki K, Suzuki A, Masuda J, et al. Increased circulating concentrations of growth-related oncogene (GRO)-alpha in patients with inflammatory bowel disease. Dig Dis Sci 2006;51:173-7.
DOI: https://doi.org/10.1007/s10620-006-3104-4
Shen YM, Xie YH, Zhao Y, Zeng Y. Pim-1 inhibitor attenuates trinitrobenzene sulphonic acid induced colitis in the mice. Clin Res Hepatol Gastroenterol 2018;42:382-6.
DOI: https://doi.org/10.1016/j.clinre.2018.01.002
da Paz Martins AS, Campos SBG, Goulart MOF, Moura FA. Extraintestinal manifestations of inflammatory bowel disease, nitroxidative stress and dysbiosis: What is the link between them? Biocell 2021;45;461-81.
DOI: https://doi.org/10.32604/biocell.2021.014332
Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014;14:329-42.
DOI: https://doi.org/10.1038/nri3661
Puleston J, Cooper M, Murch S, Bid K, Makh S, Ashwood P, et al. A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease. Aliment Pharmacol Ther 2005;21:109-20.
DOI: https://doi.org/10.1111/j.1365-2036.2004.02262.x
Akiyama T, Oishi K, Wullaert A. Bifidobacteria prevent tunicamycin-induced endoplasmic reticulum stress and subsequent barrier disruption in human intestinal epithelial caco-2 monolayers. PLoS One 2016;11:e0162448.
DOI: https://doi.org/10.1371/journal.pone.0162448
Cao SS, Zimmermann EM, Chuang BM, Song B, Nwokoye A, Wilkinson JE, et al. The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice. Gastroenterology 2013;144:989-1000.
DOI: https://doi.org/10.1053/j.gastro.2013.01.023
Darling NJ, Cook SJ. The role of MAPK signaling pathways in the response to endoplasmic reticulum stress. Biochim Biophys Acta 2014;1843:2150-63.
DOI: https://doi.org/10.1016/j.bbamcr.2014.01.009
Lee JW, Wang P, Kattah MG, Youssef S, Steinman L, DeFea K, et al. Differential regulation of chemokines by IL-17 in colonic epithelial cells. J Immunol 2008;181:6536-45.
DOI: https://doi.org/10.4049/jimmunol.181.9.6536
Ethics Approval
All animal experiments were reviewed and approved by the Institutional Animal Care Committee of Changsha Central Hospital (Approval No. 20200512)Rights
Natural Science foundation of Hunan Province of China (No. 2019JJ40319), Project of Hunan Province, Department of Health (No. B2019142), Project of Changsha Science and Technology Bureau (No. kq2004167), and Hunan Science and Technology Innovation Plan Project (No. 2020SK53306)How to Cite
Long, Y., Zhao, Y., Ma, X., Zeng, Y., Hu, T., Wu, W., … Shen, Y. (2022). Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway. European Journal of Histochemistry, 66(2). https://doi.org/10.4081/ejh.2022.3415
Copyright (c) 2022 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Francesca Diomede, Maria Zingariello, Marcos F.X.B. Cavalcanti, Ilaria Merciaro, Jacopo Pizzicannella, Natalia de Isla, Sergio Caputi, Patrizia Ballerini, Oriana Trubiani, MyD88/ERK/NFkB pathways and pro-inflammatory cytokines release in periodontal ligament stem cells stimulated by Porphyromonas gingivalis , European Journal of Histochemistry: Vol. 61 No. 2 (2017)
- M. Artico, E. Bronzetti, B. Ionta, M. Bruno, A. Greco, G. Ruoppolo, A. De Virgilio, L. Longo, M. De Vincentiis, Reinke's Edema: investigations on the role of MIB-1 and hepatocyte growth factor , European Journal of Histochemistry: Vol. 54 No. 3 (2010)
- Ermanna Turano, Federica Virla, Ilaria Scambi, Sylwia Dabrowska, Oluwamolakun Bankole, Raffaella Mariotti, Adipose mesenchymal stem cells-derived extracellular vesicles exert their preferential action in damaged central sites of SOD1 mice rather than peripherally , European Journal of Histochemistry: Vol. 68 No. 3 (2024)
- Jacopo J.V. Branca, Donatello Carrino, Ferdinando Paternostro, Massimo Gulisano, Matteo Becatti, Lorenzo Di Cesare Mannelli, Alessandra Pacini, Antioxidant support to ameliorate the oxaliplatin-dependent microglial alteration: morphological and molecular study , European Journal of Histochemistry: Vol. 65 No. s1 (2021): Special Collection on Advances in Neuromorphology in Health and Disease
- Kazuhiko Hashimoto, Shunji Nishimura, Tomohiko Ito, Masao Akagi, Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas , European Journal of Histochemistry: Vol. 65 No. 3 (2021)
- Proshanta Roy, Ilenia Martinelli, Michele Moruzzi, Federica Maggi, Consuelo Amantini, Maria Vittoria Micioni Di Bonaventura, Carlo Cifani, Francesco Amenta, Seyed Khosrow Tayebati, Daniele Tomassoni, Ion channels alterations in the forebrain of high-fat diet fed rats , European Journal of Histochemistry: Vol. 65 No. s1 (2021): Special Collection on Advances in Neuromorphology in Health and Disease
- A.J.W. Pinto, I.F.G. de Amorim, L.J. Pinheiro, I.M.V.M. Madeira, C.C. Souza, H. Chiarini-Garcia, M.V. Caliari, W.L. Tafuri, Glycol methacrylate embedding for the histochemical study of the gastrointestinal tract of dogs naturally infected with Leishmania infantum , European Journal of Histochemistry: Vol. 59 No. 4 (2015)
- N. Accart, J. Dawson, F. Kolbinger, I. Kramer, N. Beckmann, Non-invasive imaging demonstrates clinical features of ankylosing spondylitis in a rat adjuvant model: a case study , European Journal of Histochemistry: Vol. 60 No. 4 (2016)
- G. Latella, A. Vetuschi, R. Sferra, S. Speca, E. Gaudio, Localization of avβ6 integrin- TGF-β1/Smad3, mTOR and PPARgg in experimental colorectal fibrosis , European Journal of Histochemistry: Vol. 57 No. 4 (2013)
- Jun Lin, Liping Jiang, Kun Guo, Ning Feng, Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages , European Journal of Histochemistry: Vol. 67 No. 1 (2023)
<< < 1 2 3 4 5 6 7 8 9 10 > >>
You may also start an advanced similarity search for this article.
