Tissue transglutaminase is involved in the inflammatory processes of active chronic gastritis

Authors

  • Giuseppe Riezzo Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Antonella Orlando Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Caterina Clemente Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Benedetta D'Attoma Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Anna Maria Valentini Department of Pathology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Raffaele Armentano Department of Pathology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Pietro Giorgio Department of Gastroenterology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Antonio Pisani Department of Gastroenterology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy
  • Francesco Russo Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology Research Hospital, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy https://orcid.org/0000-0003-0538-6072

DOI:

https://doi.org/10.2298/ABS210412026R

Keywords:

Chronic gastritis, Inflammation, Interleukin, Transglutaminase

Abstract

Paper description:

  • Transglutaminase 2 exerts multifunctional activities and acts as an inflammation marker produced by activated macrophages in several chronic conditions, including gastritis.
  • The concentrations of transglutaminase 2 and inflammation markers, as well as macrophage score, were measured in the supernatant of gastric antrum biopsies.
  • Transglutaminase 2, interleukins 8-10, tumor necrosis factor-α and toll-like receptor-4 were significantly higher in active than inactive chronic gastritis, while interleukin-6 was significantly lower in the active form. The macrophage score and interleukin-10 correlated positively.
  • Transglutaminase 2 is involved in the pathophysiology of chronic gastritis, specifically the active one. Its inhibition could prevent the progression of gastritis.

Abstract: Since tissue transglutaminase-2 (TG2) can represent a marker of inflammation for some gastrointestinal (GI) diseases, we aimed to evaluate TG2 and inflammatory markers’ mucosal content in gastric antrum biopsies to shed light on the histological and biochemical background of chronic gastritis inflammation. Fifty-one of 78 patients who underwent upper GI endoscopy (UGIE) for dyspeptic symptoms, had a gastric biopsy. The symptom profile was assessed by a GI symptom rating scale (GSRS) score. Thirty-five patients (69%) showed chronic gastritis. TG2, interleukin-6 (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, lipopolysaccharides (LPS) and toll-like receptor (TLR)-4 were evaluated in serum and the culture medium of gastric biopsies. TG2, IL-8, IL-10, TLR-4 and TNF-α were significantly higher in active chronic gastritis than in the inactive one and were linked to macrophage concentration. IL-6 was significantly lower in the active form of chronic gastritis than in the inactive one and negatively correlated with TG2. Lastly, IL-10 significantly correlated with the macrophage score. TG2 can exert an active role in chronic gastritis pathogenesis by cooperating with different markers of inflammation. It seems that TG2 can represent a possible therapeutic target for modulating inflammation and disease progression.

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References

Zhuang R, Khosla C. Substrates, inhibitors, and probes of mammalian transglutaminase 2. Anal Biochem. 2020;591:113560. https://doi.org/10.1016/j.ab.2019.113560

Lee CS, Park HH. Structural aspects of transglutaminase 2: functional, structural, and regulatory diversity. Apoptosis. 2017;22(9):1057-68. https://doi.org/10.1007/s10495-017-1396-9

Szondy Z, Korponay-Szabó I, Király R, Sarang Z, Tsay GJ. Transglutaminase 2 in human diseases. Biomedicine (Taipei). 2017;7(3):1-13. https://doi.org/10.1051/bmdcn/2017070315

Lee CS, Park HH. Structural aspects of transglutaminase 2: functional, structural, and regulatory diversity. Apoptosis 2017;22(9):1057-68. https://doi.org/10.1007/s10495-017-1396-9

Di Sabatino A, Vanoli A, Giuffrida P, Luinetti O, Solcia E, Corazza GR. The function of tissue transglutaminase in celiac disease. Autoimmun Rev. 2012;11(10):746-53. https://doi.org/10.1016/j.autrev.2012.01.007

Maglio M, Ziberna F, Aitoro R Discepolo V, Lania G, Vassi V, Miele E, Not Tarcisio, Troncone R, Auricchio R. Intestinal production of anti-tissue transglutaminase 2 antibodies in patients with diagnosis other than celiac disease. Nutrients. 2017;9(10):1050. https://doi.org/10.3390/nu9101050

Das P, Rawat R, Verma AK, Singh G, Vallonthaiel AG, Yadav R, Gahlot GPS, Dinda AK, Ahuja V, Datta Gupta S, Agarwal SK, Makharia GK. Immunohistochemical expression of antitissue transglutaminase 2 in tissue injuries: an interpretation beyond celiac disease. Appl Immunohistochem Mol Morphol. 2018;26(6):425-30. https://doi.org/10.1097/pai.0000000000000430

Sipponen P, Maaroos HI. Chronic Gastritis. Scand J Gastroenterol. 2015;50(6):657-67.

Reshetnyak VI, Burmistrov AI, Maev IV. Helicobacter pylori: Commensal, symbiont or pathogen? World J Gastroenterol. 2021;27(7):545-60. https://doi.org/10.3748/wjg.v27.i7.545

Şenocak Taşçı E, Akbaş T. The Relationship between the Sydney Classification and the First-Line Treatment Efficacy in Helicobacter-Associated Gastritis. Med Princ Pract. 2020;29(6):551-7. https://doi.org/10.1159/000508248

Botezatu A, Bodrug N. Chronic atrophic gastritis: an update on diagnosis. Med Pharm Rep. 2021;94(1):7-14.

Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World Gastroenterol. 2012;18(12):1279-85. https://doi.org/10.3748/wjg.v18.i12.1279

Michigami Y, Watari J, Ito C, Nakai K, Yamasaki T, Kondo T, Kono T, Tozawa K, Tomita T, Oshima T, Fukui H, Morimoto T, Das KM, Miwa H. Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis. Sci Rep. 2018;8(1):14369. https://doi.org/10.1038/s41598-018-32717-3

Nie S, Yuan Y. The Role of Gastric Mucosal Immunity in Gastric Diseases. J Immunol Res. 2020;2020:7927054.

Pina Dore M, Pes GM, Errigo A, Manca A, Realdi G. Tissue transglutaminase activity in human gastric mucosa according to Helicobacter Pylori Infection. Exp Biol Med. 2018;243(15-16):1161-4. https://doi.org/10.1177/1535370218819423

Nordenstedt H, Graham DY, Kramer JR, Rugge M, Verstovsek G, Fitzgerald S, Alsarraj A, Shaib Y, Velez ME, Abraham N, Anand B, Cole R, El-Serag HB. Helicobacter pylori-negative gastritis: prevalence and risk factors. Am J Gastroenterol. 2013;108(1):65-71. https://doi.org/10.1038/ajg.2012.372

Chrobok NL, Sestito C, Wilhelmus MM, Drukarch B, Van Dam AM. Is monocyte- and macrophage-derived tissue transglutaminase involved in inflammatory processes? Amino Acids. 2017;49(3):441-52. https://doi.org/10.1007/s00726-016-2334-9

Kulich KR, Madisch A, Pacini F, Piqué JM, Regula J, Van Rensburg CJ, Ujszászy L, Carlsson J, Halling K, Wiklund IK. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008;6:12. https://doi.org/10.1186/1477-7525-6-12

Rugge M, Pennelli G, Pilozzi E, Fassan M, Ingravallo G, Russo VM, Di Mario F; Gruppo Italiano Patologi Apparato Digerente (GIPAD); Società Italiana di Anatomia Patologica e Citopatologia Diagnostica/International Academy of Pathology, Italian division (SIAPEC/IAP). Gastritis: the histology report. Dig Liver Dis. 2011;43(Suppl. 4):S373-84. https://doi.org/10.1016/s1590-8658(11)60593-8

Rugge M, Savarino E, Sbaraglia M, Bricca L, Malfartheiner P. Gastritis: The clinico-pathological spectrum. Dig Liver Dis. 2021; https://doi.org/10.1016/j.dld.2021.03.007

Magen E, Schlesinger M, Ben-Zion I, Vardy D. Helicobacter pylori infection in patients with selective immunoglobulin E deficiency. World J Gastroenterol. 2015;21(1):240-5.

Carroccio A, Di Prima L, Pirrone G, Scalici C, Florena AM, Gasparin M, Tolazzi G, Gucciardi A, Sciumè C, Iacono G. Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis. Clin Chem. 2006;52(6):1175-80. https://doi.org/10.1373/clinchem.2005.061366

Russo F, Chimienti G, Clemente C, Riezzo G, D’attoma B, Martulli M. Gastric activity and gut peptides in patients with functional dyspepsia: postprandial distress syndrome versus epigastric pain syndrome. J Clin Gastroenterol. 2017;51(2):136-44. https://doi.org/10.1097/mcg.0000000000000531

Tatsukawa H, Takeuchi T, Shinoda Y, Hitomi K. Identification and characterization of substrates crosslinked by transglutaminases in liver and kidney fibrosis. Anal Biochem. 2020;604:113629. https://doi.org/10.1016/j.ab.2020.113629

Lu Y, Rong J, Lai Y, Tao L, Yuan X, Shu X. The degree of helicobacter pylori infection affects the state of macrophage polarization through crosstalk between ROS and HIF-1α. Oxid Med Cell Longev. 2020;2020:5281795. https://doi.org/10.1155/2020/5281795

Zavros Y, Eaton KA, Kang W, Rathinavelu S, Katukuri V, Kao JY, Samuelson LC, Merchant JL. Chronic gastritis in the hypochlorhydric gastrin-deficient mouse progresses to adenocarcinoma. Oncogene. 2005;24(14):2354-66. https://doi.org/10.1038/sj.onc.1208407

Bayardo M, Punzi F, Bondar C, Chopita N, Chirdo F. Transglutaminase 2 expression is enhanced synergistically by interferon-γ and tumour necrosis factor-α in human small intestine. Clin Exp Immunol. 2012;168(1):95-104. https://doi.org/10.1111/j.1365-2249.2011.04545.x

Oh K, Lee OY, Park Y, Seo MW, Lee DS. IL-1β induces IL-6 production and increases invasiveness and estrogen-independent growth in a TG2-dependent manner in human breast cancer cells. BMC Cancer. 2016;16(1):724. https://doi.org/10.1186/s12885-016-2746-7

Eligini S, Fiorelli S, Tremoli E, Colli S. Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors. Nutr Metab Cardiovasc Dis. 2016;26(10):922-30. https://doi.org/10.1016/j.numecd.2016.05.011

Lee HS, Park DE, Bae B, Oh K, Jung JW, Lee DS, Kim IG, Cho SH, Kang HR. Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages. Immun Inflamm Dis. 2021; https://doi.org/10.1002/iid3.442

Wong JH, Ho KH, Nam S, Hsu WL, Lin CH, Chang CM, Wang JY, Chang WC. Store-operated Ca2+ Entry Facilitates the Lipopolysaccharide-induced Cyclooxygenase-2 Expression in Gastric Cancer Cells. Sci Rep. 2017;7(1):12813. https://doi.org/10.1038/s41598-017-12648-1

Nemati M, Larussa T, Khorramdelazad H, Mahmoodi M, Jafarzadeh A. Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection. Life Sci. 2017;178:17-29. https://doi.org/10.1016/j.lfs.2017.04.006

Slomiany BL, Slomiany A. Role of LPS-elicited signaling in triggering gastric mucosal inflammatory responses to H. pylori: modulatory effect of ghrelin. Inflammopharmacology. 2017;25(4):415-29. https://doi.org/10.1007/s10787-017-0360-1

Lamb A, Chen J, Blanke SR, Chen LF. Helicobacter pylori activates NF-κB by inducing Ubc13-mediated ubiquitination of lysine 158 of TAK1. J Cell Biochem. 2013;114(10):2284-92. https://doi.org/10.1002/jcb.24573

Bagheri N, Azadegan-Dehkordi F, Sanei H, Taghikhani A, Rahimian G, Salimzadeh L, Hashemzadeh-Chaleshtori M, Rafieian-kopaei M, Shirzad M, Shirzad H. Associations of a TLR4 single-nucleotide polymorphism with H. pylori associated gastric diseases in Iranian patients. Clin Res Hepatol Gastroenterol. 2014;38(3):366-71. https://doi.org/10.1016/j.clinre.2013.12.004

Tsai CC, Chen TY, Tsai KJ, Lin MW, Hsu CY, Wu DC, Tsai EM, Hsieh TH. NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-associated gastric cancer. Biomed Pharmacother. 2020;132:110869. https://doi.org/10.1016/j.biopha.2020.110869

Tanaka T, Narazaki M, Masuda K, Kishimoto T. Regulation of Il-6 in immunity and diseases. Adv Exp Med Biol. 2016;941:79-88.

Nahid-Samiei M, Rahimian G, Shafigh M, Taheri F, Karami-Hurestani M, Sanaei MJ, Heshmati M, Bagheri N. Enhanced Frequency of CD19+IL-10+B Cells in Human Gastric Mucosa Infected by Helicobacter pylori. Am J Med Sci. 2020;359(6):347-53. https://doi.org/10.1016/j.amjms.2020.03.019

Oh K, Moon HG, Lee DS, Yoo YB. Tissue transglutaminase-Interleukin-6 axis facilitates peritoneal tumor spreading and metastasis of human ovarian cancer cells. Lab Anim Res. 2015;31(4):188-97. https://doi.org/10.5625/lar.2015.31.4.188

Lee HT, Huang CH, Chen WC, Tsai CS, Chao YL, Liu SH, Chen JH, Wu YY, Lee YJ. Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells. Oncol Res. 2018;26(8):1175-82. https://doi.org/10.3727/096504018x15149761920868

Tabolacci C, De Martino A, Mischiati C, Feriotto G, Beninati S. The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression. Med Sci (Basel). 2019;7(2):19. https://doi.org/10.3390/medsci7020019

Lei Z, Chai N, Tian M, Zhang Y, Wang G, Liu J, Tian Z, Yi X, Chen D, Li X, Yu P, Hu H, Xu B, Jian C, Bian Z, Guo H, Wang J, Peng S, Nie Y, Huang N, Hu S, Wu K. Novel peptide GX1 inhibits angiogenesis by specifically binding to transglutaminase-2 in the tumorous endothelial cells of gastric cancer. Cell Death Dis. 2018;9(6):579. https://doi.org/10.1038/s41419-018-0594-x

Kim SY. New Insights into Development of Transglutaminase 2 Inhibitors as Pharmaceutical Lead Compounds. Med Sci (Basel). 2018;6(4):87.

Shiota S, Thrift AP, Green L, Shah R, Verstovsek G, Rugge M, Graham DY, El-Serag HB. Clinical Manifestations of Helicobacter pylori-Negative Gastritis. Clin Gastroenterol Hepatol. 2017;15(7):1037-1046.e3. https://doi.org/10.1016/j.cgh.2017.01.006

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Published

2021-10-12

How to Cite

1.
Riezzo G, Orlando A, Clemente C, D’Attoma B, Valentini AM, Armentano R, Giorgio P, Pisani A, Russo F. Tissue transglutaminase is involved in the inflammatory processes of active chronic gastritis. Arch Biol Sci [Internet]. 2021Oct.12 [cited 2021Dec.8];73(3):331-9. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/6500

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