Original Article
 

Evaluating the MicroRNA Expression of IL-35 and IL-37 in Helicobacter Pylori-infected Patients with Gastritis and Gastric Ulcer

Abstract

Interleukin (IL)-35 and IL-37 are two anti-inflammatory cytokines. IL-35 inhibits the development of T-effector cells such as Th1, and Th17; while increasing regulatory T cells (Tregs). IL-37 causes the suppression of inflammatory cytokines. Regarding the positive impact of Helicobacter pylori (H. pylori) infection on inflammation and considering the anti-inflammatory effects of IL-35 and IL-37, this study aimed to evaluate the expression of these two cytokines in H. pylori-infected patients with gastrointestinal problems.
The case group consisted of H. pylori-infected individuals with gastric ulcer and/or gastritis (n=50) and the control group consisted of cases with gastric ulcer and/or gastritis non-H. pylori-infected (n=50). Sampling and classification of patients were based on pathology findings. A real-time polymerase chain reaction was performed for evaluating the IL-35 and IL-37 expression levels.
pylori-infected gastritis patients showed lower expression of IL-35 and IL-37 than the non-infected group. There was a significant difference between the expression levels of IL-35 and IL-37 in patients with gastric ulcers and/or gastritis who were infected and non-infected by H. pylori. There were no significant differences in the expression level of IL-35 and IL-37 in H. pylori-infected patients with gastric ulcer or gastritis.
Interleukins 37 and 35 were less expressed in patients with H. pylori-infection. In differentiation between patients with gastrointestinal symptoms who have H. pylori infection or with similar symptoms who do not have H. pylori-infection, mentioned interleukins can be used as diagnostic markers.

1. Marshall B, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;323(8390):1311-5.
2. Teimoorian F, Ranaei M, Hajian Tilaki K, Shokri Shirvani J, Vosough Z. Association of Helicobacter pylori infection with colon cancer and adenomatous polyps. Iran J Patholog. 2018;13(3):325-32.
3. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterology. 1998; 115(3):642-8.
4. Peek RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nature Reviews Cancer. 2002; 2(1):28-37.
5. Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Ann Rev Microbiol. 2000;54(1):615-40.
6. Denic M, Touati E, De Reuse H. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2020;25:e12736.
7. Olofsson A, Vallström A, Petzold K, Tegtmeyer N, Schleucher J, Carlsson S, et al. Biochemical and functional characterization of Helicobacter pylori vesicles. Mol Microbiol. 2010;77(6):1539-55.
8. Youssefi M, Ghazvini K, Farsiani H, Tafaghodi M, Keikha M. A systematic review and meta-analysis of outcomes of infection with Helicobacter pylori dupA+ strains in Iranian patients. Gene Reports. 2020;19(2020):100650.
9. Emmanuel AB, Chukwuemeka NA, Taye OG, Chinonso AA, Adejoh IP. Inhibition of gastric acid secretion is a probable mechanism underlying the anti-ulcer activity of Alchornea cordifolia (Schumach. & Thonn.) Int J Adv Multidisciplin Res Rev. 2020;7(12):24-30.
10. Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23(4):713-39.
11. El‐Zimaity H, Riddell RH. Beyond Helicobacter: dealing with other variants of gastritis—an algorithmic approach. Histopathology. 2021;78(1):48-69.
12. Musumba C, Jorgensen A, Sutton L, Eker D, Moorcroft J, Hopkins M, et al. The relative contribution of NSAIDs and Helicobacter pylori to the etiology of endoscopically‐diagnosed peptic ulcer disease: observations from a tertiary referral hospital in the UK between 2005 and 2010. Aliment Pharmacol Ther. 2012;36(1):48-56.
13. Konturek P, Konturek S, Brzozowski T. Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 2009;60(3):3-21.
14. Hasegawa H, Mizoguchi I, Chiba Y, Ohashi M, Xu M, Yoshimoto T. Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family. Front Immunol. 2016;7(2016):479.
15. Chaturvedi V, Collison LW, Guy CS, Workman CJ, Vignali DA. Cutting edge: human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J Immunol. 2011;186(12):6661-6.
16. Ye S, Wu J, Zhou L, Lv Z, Xie H, Zheng S. Interleukin-35: the future of hyperimmune-related diseases? J Interferon Cytokine Res. 2013;33(6):285-91.
17. Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010;11(11):1014-22.
18. Dunn E, Sims JE, Nicklin MJ, O'Neill LA. Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol. 2001;22(10):533-6.
19. Warren JR. Gastric pathology associated with Helicobacter pylori. Gastroenterol Clin North Am. 2000; 29(3):705-51.
20. Ansari S, Yamaoka Y. Helicobacter pylori virulence factor cytotoxin-associated gene A (CagA)-mediated gastric pathogenicity. Int J Mol Sci. 2020;21(19):7430-5.
21. Zhang C, Yamada N, Wu YL, Wen M, Matsuhisa T, Matsukura N. Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients. World J Gastroenterol. 2005;11(7):976-81.
22. Azadegan-Dehkordi F, Bagheri N, Shirzad M, Sanei MH, Hashemzadeh-Chaleshtori M, Rafieian-Kopaei M, et al. Correlation between mucosal IL-6 mRNA expression level and virulence factors of Helicobacter pylori in Iranian adult patients with chronic gastritis. Jundishapur J Microbiol. 2015;8(8):e21701.
19. Zandian MMK, Allen SJ, Dumitrascu O, Kuo JZ, Ghiasi H. Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2. Gene Therapy. 2011;18(7):734-42.
20. Liu J-Q LZ, Zhang X, Shi Y, Talebian F, Carl JW. Increased Th17 and regulatory T cell responses in EBV-induced gene 3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis. J Immunol. 2012;188(7):3099-106.
21. Sawant DV, Hamilton K, Vignali DA. Interleukin-35: expanding its job profile. J Int Cytokine Res. 2015;35(7):499-512.
22. Floss DM, Moll JM, Scheller J. IL-12 and IL-23-close relatives with structural homologies but distinct immunological functions. Cells. 2020;9(10):2184.
22. Boraschi D, Lucchesi D, Hainzl S, Leitner M, Maier E, Mangelberger D, et al. IL-37: a new anti-inflammatory cytokine of the IL-1 family. Eur Cytokine Netw. 2011;22(3):127-47.
23. Floss DM, Schönberg M, Franke M, Horstmeier FC, Engelowski E, Schneider A, et al. IL-6/IL-12 cytokine receptor shuffling of extra- and intracellular domains reveals canonical STAT activation via synthetic IL-35 and IL-39 signaling. Sci Rep. 2017;7(1):15172-9.
24. Dewayani A, Fauzia KA, Alfaray RI, Waskito LA, Doohan D, Rezkitha YA, et al. The roles of IL-17, IL-21, and IL-23 in the Helicobacter pylori Infection and gastrointestinal inflammation: a review. Toxins. 2021;13(5):315.
25. Sayar R, Shokri Shirvani J, Hajian-Tilaki K, Vosough Z, Ranaei M. The negative association between inflammatory bowel disease and Helicobacter pylori seropositivity. Caspian J Int Med. 2019;10(2):217-2.
Files
IssueVol 21 No 1 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v21i1.8609
Keywords
Gastritis Helicobacter pylori Human interleukin-35 Human IL37 protein Stomach ulcer

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ahmadnia Z, Ranaee M, Mohammadi Abandansari R, Bagheri N, Shirzad H. Evaluating the MicroRNA Expression of IL-35 and IL-37 in Helicobacter Pylori-infected Patients with Gastritis and Gastric Ulcer. Iran J Allergy Asthma Immunol. 2022;21(1):20-26.