Skip to main content

Advertisement

SpringerLink
Log in

Mitigation of Gliadin-Induced Inflammation and Cellular Damage by Curcumin in Human Intestinal Cell Lines

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Wheat is a major diet from many years; apart from its nutritious value, the wheat protein gliadin is responsible for many inflammatory diseases like celiac disease (CD), and non-celiac gluten sensitivity (NCGS). In this study, the gliadin-induced inflammation and associated cellular damage along with the protective role of curcumin was evaluated using human intestinal cell lines (HCT-116 and HT-29) as a model. Cells were cultured and exposed to 160 μg/ml of gliadin, 100 μM H2O2, and 10 μM curcumin (3 h pretreatment) followed by the assessment of inflammation. Spectrophotometric methods, real-time-PCR, ELISA, Western blotting, and confocal microscopy techniques were used to assess inflammatory markers such as advanced oxidation protein products (AOPPs) level, activity of myeloperoxidase (MPO) and NADPH oxidase (NOX), cytokines, and cell damage markers. The results show that gliadin increases the AOPPs level and the activity of MPO and NOX expression. It enhances inflammation by increasing expression of pro-inflammatory cytokines, altered expression of anti-inflammatory, and regulatory cytokines. It exacerbates the cellular damage by increasing MMP-2 and 9 and decreasing integrin α and β expression. Gliadin promotes disease pathogenesis by inducing the inflammation and cellular damage which further alter the cellular homeostasis. The pretreatment of curcumin counteracts the adverse effect of gliadin and protect the cells via diminishing the inflammation and help the cell to regain the cellular morphology suggesting phytochemical-based remedial interventions against wheat allergies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Shewry, Peter R., Nigel G. Halford, Peter S. Belton, and Arthur S. Tatham. 2002. The structure and properties of gluten: an elastic protein from wheat grain. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 357 (1418): 133–142.

    CAS  Google Scholar 

  2. Balakireva, Anastasia V., and Andrey A. Zamyatnin. 2016. Properties of gluten intolerance: gluten structure, evolution, pathogenicity and detoxification capabilities. Nutrients 8 (10): 644.

    Article  Google Scholar 

  3. Molberg, Øyvind, Stephen N. Mcadam, Roman Körner, Hanne Quarsten, Christel Kristiansen, Lars Madsen, Lars Fugger, Helge Scott, Ove Norén, and Peter Roepstorff. 1998. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nature Medicine 4 (6): 713–717.

    Article  CAS  Google Scholar 

  4. Mayassi, Toufic, Kristin Ladell, Herman Gudjonson, James E. McLaren, Dustin G. Shaw, Mai T. Tran, Jagoda J. Rokicka, Ian Lawrence, Jean-Christophe Grenier, and Vincent van Unen. 2019. Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease. Cell 176 (5): 967–981 e919.

    Article  CAS  Google Scholar 

  5. Gupta, Kunj Bihari, Shishir Upadhyay, Ram Gopal Saini, Anil K Mantha, and Monisha Dhiman. 2018. Inflammatory response of gliadin protein isolated from various wheat varieties on human intestinal cell line. Journal of Cereal Science 81:91-98.

  6. Thakur, Shweta, Monisha Dhiman, and Anil K. Mantha. 2018. APE1 modulates cellular responses to organophosphate pesticide-induced oxidative damage in non-small cell lung carcinoma A549 cells. Molecular and Cellular Biochemistry 441 (1-2): 201–216.

    Article  CAS  Google Scholar 

  7. Levrand, Sandra, Benoît Pesse, François Feihl, Bernard Waeber, Pal Pacher, Joëlle Rolli, Marie-Denise Schaller, and Lucas Liaudet. 2005. Peroxynitrite is a potent inhibitor of NF-κB activation triggered by inflammatory stimuli in cardiac and endothelial cell lines. Journal of Biological Chemistry 280 (41): 34878–34887.

    Article  CAS  Google Scholar 

  8. Dhiman, Monisha, Jose Guillermo Estrada-Franco, Jasmine M. Pando, Francisco J. Ramirez-Aguilar, Heidi Spratt, Sara Vazquez-Corzo, Gladys Perez-Molina, Rosa Gallegos-Sandoval, Roberto Moreno, and Nisha Jain Garg. 2009. Increased myeloperoxidase activity and protein nitration are indicators of inflammation in patients with Chagas' disease. Clinical and Vaccine Immunology 16 (5): 660–666.

    Article  CAS  Google Scholar 

  9. Baskol, Gülden, Hüseyin Demir, Mevlut Baskol, Eser Kilic, Filiz Ates, Cigdem Karakukcu, and Muzaffer Ustdal. 2006. Investigation of protein oxidation and lipid peroxidation in patients with rheumatoid arthritis. Cell Biochemistry and Function: Cellular biochemistry and its modulation by active agents or disease 24 (4): 307–311.

    Article  CAS  Google Scholar 

  10. Vaday, Gayle G., Donna M. Peehl, Pournima A. Kadam, and Diana M. Lawrence. 2006. Expression of CCL5 (RANTES) and CCR5 in prostate cancer. The Prostate 66 (2): 124–134.

    Article  CAS  Google Scholar 

  11. Cholia, Ravi P., Monisha Dhiman, Raj Kumar, and Anil K. Mantha. 2018. Oxidative stress stimulates invasive potential in rat C6 and human U-87 MG glioblastoma cells via activation and cross-talk between PKM2, ENPP2 and APE1 enzymes. Metabolic Brain Disease 33 (4): 1307–1326.

    Article  CAS  Google Scholar 

  12. Upadhyay, Shishir, Anil K Mantha, and Monisha Dhiman. 2020. Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes. Journal of Ethnopharmacology:112690.

  13. Monguzzi, Erika, Laura Marabini, Luca Elli, Valentina Vaira, Stefano Ferrero, Francesca Ferretti, Federica Branchi, Gabriella Gaudioso, Alice Scricciolo, and Vincenza Lombardo. 2019. Gliadin effect on the oxidative balance and DNA damage: An in-vitro, ex-vivo study. Digestive and Liver Disease 51 (1): 47–54.

    Article  CAS  Google Scholar 

  14. Qiao, Shuo-Wang, Melinda Ráki, Kristin S. Gunnarsen, Geir-Åge Løset, Knut E.A. Lundin, Inger Sandlie, and Ludvig M. Sollid. 2011. Posttranslational modification of gluten shapes TCR usage in celiac disease. The Journal of Immunology 187 (6): 3064–3071.

    Article  CAS  Google Scholar 

  15. Kagnoff, Martin F. 2007. Celiac disease: pathogenesis of a model immunogenetic disease. The Journal of Clinical Investigation 117 (1): 41–49.

    Article  CAS  Google Scholar 

  16. McAllister, Christopher S., and Martin F. Kagnoff. 2012. The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet. Seminars in Immunopathology 4 (4): 581–600.

    Article  Google Scholar 

  17. Kristjánsson, Gudjon, Per Venge, Alkwin Wanders, Lars Lööf, and Roger Hällgren. 2004. Clinical and subclinical intestinal inflammation assessed by the mucosal patch technique: studies of mucosal neutrophil and eosinophil activation in inflammatory bowel diseases and irritable bowel syndrome. Gut 53 (12): 1806–1812.

    Article  Google Scholar 

  18. Peterson, Christer G.B., Elisabeth Eklund, Yesuf Taha, Yngve Raab, and Marie Carlson. 2002. A new method for the quantification of neutrophil and eosinophil cationic proteins in feces: establishment of normal levels and clinical application in patients with inflammatory bowel disease. The American Journal of Gastroenterology 97 (7): 1755–1762.

    Article  CAS  Google Scholar 

  19. Gryszczyńska, Bogna, Dorota Formanowicz, Magdalena Budzyń, Maria Wanic-Kossowska, Elżbieta Pawliczak, Piotr Formanowicz, Wacław Majewski, Krzysztof Wojciech Strzyżewski, Magdalena P. Kasprzak, and Maria Iskra. 2017. Advanced oxidation protein products and carbonylated proteins as biomarkers of oxidative stress in selected atherosclerosis-mediated diseases. BioMed Research International 2017. https://doi.org/10.1155/2017/4975264.

  20. Sayar, Ersin, Sebahat Özdem, Gülbahar Uzun, Ali İşlek, Aygen Yılmaz, and Reha Artan. 2015. Total oxidant status, total antioxidant capacity and ischemia modified albumin levels in children with celiac disease. Turkish Journal of Pediatrics 57 (5): 498–503.

    Google Scholar 

  21. Panday, Arvind, Malaya K. Sahoo, Diana Osorio, and Sanjay Batra. 2015. NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cellular & Molecular Immunology 12 (1): 5–23.

    Article  CAS  Google Scholar 

  22. Xu, Qing, Swati Choksi, Qu Jianhui, Jonathan Jang, Moran Choe, Botond Banfi, John F. Engelhardt, and Zheng-Gang Liu. 2016. NADPH Oxidases are essential for macrophage differentiation. The Journal of Biological Chemistry 291 (38): 20030–20041.

    Article  CAS  Google Scholar 

  23. Krause, Karl-Heinz, and Karen Bedard. 2008. NOX enzymes in immuno-inflammatory pathologies. In Seminars in Immunopathology30(3):193-194..

  24. Daulatzai, Mak A. 2015. Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 14 (1): 110–131.

    CAS  Google Scholar 

  25. Patlevič, Peter, Janka Vašková, Pavol Švorc Jr, Ladislav Vaško, and Pavol Švorc. 2016. Reactive oxygen species and antioxidant defense in human gastrointestinal diseases. Integrative Medicine Research 5 (4): 250–258.

  26. Antvorskov, Julie C., Petra Fundova, Karsten Buschard, and David P. Funda. 2013. Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice. Immunology 138 (1): 23–33.

    Article  CAS  Google Scholar 

  27. Forsberg, Göte, Olle Hernell, Sten Hammarström, and Marie-Louise Hammarström. 2007. Concomitant increase of IL-10 and pro-inflammatory cytokines in intraepithelial lymphocyte subsets in celiac disease. International Immunology 19 (8): 993–1001.

    Article  CAS  Google Scholar 

  28. Kumar, B.V. Mohan, M. Vijaykrishnaraj, Nawneet K. Kurrey, Vijay S. Shinde, and P. Prabhasankar. 2019. Prolyl endopeptidase-degraded low immunoreactive wheat flour attenuates immune responses in Caco-2 intestinal cells and gluten-sensitized BALB/c mice. Food and Chemical Toxicology 129: 466–475.

    Article  Google Scholar 

  29. Abadie, Valérie, and Bana Jabri. 2014. IL-15: a central regulator of celiac disease immunopathology. Immunological Reviews 260 (1): 221–234.

    Article  CAS  Google Scholar 

  30. Mention, Jean-Jacques, Mélika Ben Ahmed, Bernadette Bègue, Ullah Barbe, Virginie Verkarre, Vahid Asnafi, Jean-frédéric Colombel, Paul-henri Cugnenc, Frank M. Ruemmele, and Elisabeth Mcintyre. 2003. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 125 (3): 730–745.

    Article  CAS  Google Scholar 

  31. Maiuri, Luigi, Carolina Ciacci, Salvatore Auricchio, Virginia Brown, Sonia Quaratino, and Marco Londei. 2000. Interleukin 15 mediates epithelial changes in celiac disease. Gastroenterology 119 (4): 996–1006.

    Article  CAS  Google Scholar 

  32. Jabri, Bana, Natacha Patey–Mariaud De Serre, Christophe Cellier, Kelly Evans, Cécile Gache, Carla Carvalho, Jean–François Mougenot, Matthieu Allez, Raymond Jian, and Pierre Desreumaux. 2000. Selective expansion of intraepithelial lymphocytes expressing the HLA-E–specific natural killer receptor CD94 in celiac disease. Gastroenterology 118 (5):867-879.

  33. Fernandez-Jimenez, Nora, Ainara Castellanos-Rubio, Leticia Plaza-Izurieta, Iñaki Irastorza, Xabier Elcoroaristizabal, Amaia Jauregi-Miguel, Tamara Lopez-Euba, Carlos Tutau, Marian M. de Pancorbo, and Juan Carlos Vitoria. 2014. Coregulation and modulation of NFκB-related genes in celiac disease: uncovered aspects of gut mucosal inflammation. Human Molecular Genetics 23 (5): 1298–1310.

    Article  CAS  Google Scholar 

  34. Przemioslo, R.T., M. Kontakou, V. Nobili, and P.J. Ciclitira. 1994. Raised pro-inflammatory cytokines interleukin 6 and tumour necrosis factor alpha in coeliac disease mucosa detected by immunohistochemistry. Gut 35 (10): 1398–1403.

    Article  CAS  Google Scholar 

  35. Sturgess, R.P., L.B. Hooper, J. Spencer, C.H. Hung, J.M. Nelufer, and P.J. Ciclitira. 1992. Effects of interferon-y and tumour necrosis factor-cu on epithelial HLA class-II expression on jejunal mucosal biopsy specimens cultured in vitro. Scandinavian Journal of Gastroenterology 27 (11): 907–911.

    Article  CAS  Google Scholar 

  36. Maiuri, Maria Chiara, Daniela De Stefano, Guido Mele, Simona Fecarotta, Luigi Greco, Riccardo Troncone, and Rosa Carnuccio. 2003. Nuclear factor κB is activated in small intestinal mucosa of celiac patients. Journal of Molecular Medicine 81 (6): 373–379.

    Article  CAS  Google Scholar 

  37. de Almeida, Natália Ellen Castilho, Franciele Grego Esteves, José Roberto Aparecido dos Santos-Pinto, Carla Peres de Paula, Anderson Ferreira da Cunha, Iran Malavazi, Mario Sergio Palma, and Edson Rodrigues-Filho. 2020. Digestion of intact gluten proteins by bifidobacterium species: reduction of cytotoxicity and proinflammatory responses. Journal of Agricultural and Food Chemistry 68 (15): 4485–4492.

    Article  Google Scholar 

  38. Wan, Fengyi, and Michael J. Lenardo. 2009. Specification of DNA binding activity of NF-κB proteins. Cold Spring Harbor Perspectives in Biology 1 (4): a000067.

    Article  Google Scholar 

  39. Liu, Ting, Lingyun Zhang, Donghyun Joo, and Shao-Cong Sun. 2017. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2 (1): 1–9.

    CAS  Google Scholar 

  40. Kárpáti, Sarolta, Miklós Sárdy, Krisztián Németh, Balázs Mayer, Neil Smyth, Mats Paulsson, and Heiko Traupe. 2018. Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation. Experimental Dermatology 27 (8): 807–814.

    Article  Google Scholar 

  41. Ciccocioppo, R., A. Di Sabatino, C. Ara, F. Biagi, M. Perilli, G. Amicosante, M.G. Cifone, and G.R. Corazza. 2003. Gliadin and tissue transglutaminase complexes in normal and coeliac duodenal mucosa. Clinical and Experimental Immunology 134 (3): 516–524.

    Article  CAS  Google Scholar 

  42. Bagatur, Yesim, Ayca Zeynep Ilter Akulke, Ajna Bihorac, Merve Erdem, and Dilek Telci. 2018. Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma. Cell Adhesion & Migration 12 (2): 138–151.

    Google Scholar 

  43. Lai, Thung-S, Robert A. Lindberg, Hua-Lin Zhou, Zishan A. Haroon, Mark W. Dewhirst, Alfred Hausladen, Y.-L. Juang, Jonathan S. Stamler, and Charles S. Greenberg. 2017. Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide. Scientific Reports 7 (1): 1–9.

    Article  Google Scholar 

  44. Ciccocioppo, Rachele, Antonio Di Sabatino, Michael Bauer, Daniela N. Della Riccia, Francesca Bizzini, Federico Biagi, Maria G. Cifone, Gino R. Corazza, and Detlef Schuppan. 2005. Matrix metalloproteinase pattern in celiac duodenal mucosa. Laboratory Investigation 85 (3): 397–407.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

KBG acknowledges the ICMR, New Delhi, for providing financial assistance in term of JRF/SRF. Central Instrumentation Laboratory (CIL) of CUPB thankfully acknowledged for confocal microscope facility. Authors are also thankful to the Honorable Vice-Chancellor for providing the necessary facilities at the Central University of Punjab, Bathinda, India.

Author information

Authors and Affiliations

  1. Department of Microbiology, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, 151401, India

    Kunj Bihari Gupta & Monisha Dhiman

  2. Department of Zoology, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, 151401, India

    Anil K. Mantha

Authors
  1. Kunj Bihari Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anil K. Mantha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monisha Dhiman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monisha Dhiman.

Ethics declarations

Conflict of Interests

The authors declare that they have no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, K.B., Mantha, A.K. & Dhiman, M. Mitigation of Gliadin-Induced Inflammation and Cellular Damage by Curcumin in Human Intestinal Cell Lines. Inflammation 44, 873–889 (2021). https://doi.org/10.1007/s10753-020-01383-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-020-01383-x

KEY WORDS

Search

Navigation