Role of vitamin D3 on IL-17 expression in colon and improvement of colonic mucosa in an inflammatory bowel disease mice model

Keywords: Inflammatory bowel disease, interleukin-17, T helper 17, vitamin D3

Abstract

Background Inflammatory bowel disease (IBD) is an inflammation due to a Th1/Th2 regulatory imbalance and a Th17/Treg transformation imbalance which then releases inflammatory mediators, such as interleukin-17. The administration of vitamin D has the potential to prevent the inflammation in IBD.

Objective To evaluate a possible role of vitamin D3 in reducing IL-17 expression and colonic mucosal repair in an IBD mice model.

Methods The study used male BALB/c mice, 8-10 weeks old, weighing 20-25 grams, divided randomly into five groups with 8 mices in each group. The experimental mice were given 5% dextran sulfate sodium (DSS) on days 1-7 to induce colitis, and then were given vitamin D3 on days 8-14. Group 1 was the control group; Group 2 was given 5% DSS; Group 3 was given 5% DSS and vitamin D3 0.2 mcg/25 g body weight; Group 4 was given 5% DSS and vitamin D3 0.4 mcg/25 g body weight; and Group 5 was given 5% DSS and vitamin D3 0.6 mcg/25 g body weight. On day 15, the mice underwent euthanasia and colonic retrieval. Parameters assessed were IL-17 expression (immunohistochemical, with monoclonal antibody against IL-17) and colonic histology improvement, using the mouse colitis histology index (MCHI) score.

Results The IL-17 expression measured by immunohistochemistry increased significantly in only 5% DSS group. There was a significant decrease in MCHI scores in the groups given vitamin D3, where the greater the dose of vitamin D3 given, the lower the MCHI score. Interleukin-17 expression had positive strong correlation with MCHI (r=0.985; P=0.002)

Conclusion The improvement of colonic mucosal damage based on MCHI score was significant in groups given vitamin D3. There is a significant correlation between IL-17 reduction and colonic mucosal repair in IBD mice.

References

1. Hegar B, Ananta Y, Rini D. Inflammatory bowel disease in Indonesian children. Paediatr Indones. 2007;47:307-12. DOI: https://doi.org/10.14238/pi47.6.2007.307-12.
2. Rosen MJ, Dhawan A, Saeed SA. 2015. Inflammatory bowel disease in children and adolescent. JAMA Pediatric. 2015;169:1053-60. DOI: https://doi.org/10.1001/jamapediatrics.2015.1982.
3. de Souza WN, Martini LA. The role of vitamin D in obesity and inflammation at adipose tissue. J Obes Metabolic Res. 2015;2;161-6. DOI: https://doi.org/10.4103/2347-9906.162350.
4. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med. 2004;229:1136–42. DOI: https://doi.org/10.1177/153537020422901108.
5. Raman M, Milestone AN, Walters JRF, Hart AL, Ghosh S. Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer. Therap Adv Gastroenterol. 2011;4:49-62. DOI: https://doi.org/10.1177/1756283X10377820.
6. Fronczuk M, Raftery AE, Yeung KY. CyNetworkBMA: a Cytoscape app for inferring gene regulatory networks. Source Code Biol Med. 2015;10:11. DOI: https://doi.org/10.1186/s13029-015-0043-5.
7. Del Pinto R, Pietropaoli D, Chandar AK, Ferri C, Cominelli F. Association between inflammatory bowel disease and vitamin D deficiency: a systematic review and meta-analysis. Inflamm Bowel Dis. 2015;21:2708-71. DOI: https://doi.org/10.1097/MIB.0000000000000546.
8. Cantorna MT. Mechanisms underlying the effect of vitamin D on the immune system. Proc Nutr Soc. 2010;69:286-9. DOI: https://doi.org/10.1017/S0029665110001722.
9. Van den Berg WB, Mc Innes IB. 2013. Th17 cells and IL-17 a focus on immunopatogenesis and immunotherapeutics. Semin Arthritis Rheum. 2013;43:158-70. DOI: https://doi.org/10.1016/j.semarthrit.2013.04.006.
10. Fitzpatrick LR. 2012. Novel pharmacological approaches for inflammatory bowel disease: targeting key intracellular pathways and the IL-23/IL-17 axis. Int J Inflam. 2012:389404. DOI: https://doi.org/10.1155/2012/389404.
11. Eichele DD, Kharbanda KK. Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J Gastroenterol. 2017; 23: 6016–29. DOI: https://doi.org/10.3748/wjg.v23.i33.6016.
12. Koelink PJ, Wildenberg ME, Stitt LW, Feagan BG, Koldijk M, van‘t Wout AB, van den Brink GR. Development of reliable, valid and responsive scoring systems for endoscopy and histology in animal models for inflammatory bowel disease. Journal of Crohn’s and Colitis. 2018;12:794-803. DOI: https://doi.org/10.1093/ecco-jcc/jjy035.
13. Kiesler P, Fuss IJ, Strober W. Experimental Models of Inflammatory Bowel Diseases. Cell Mol Gastro-enterol Hepatol. 2015;1:154-70. DOI: https://doi.org/10.1016/j.jcmgh.2015.01.006.
14. Perse M, Cerar A. Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol, 2012;2012:718617. DOI: https://doi.org/10.1155/2012/718617.
15. Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014; 104: Unit–15.25. DOI: https://doi.org/10.1002/0471142735.im1525s104.
16. Abdelmegid AM, Abdo FK, Ahmed FE, Kattaia A. Therapeutic effect of gold nanoparticles on DSS-induced ulcerative colitis in mice with reference to interleukin-17 expression. Sci Rep. 2019 9:10176. DOI: https://doi.org/10.1038/s41598-019-46671-1.
17. Sun Y, Zhao Q, Liu T. Intestinal vitamin D receptor signaling ameliorates dextran sulfate sodium-induced colitis by suppressing necroptosis of intestinal epithelial cells. The FASEB Journal. 2020;34:13494-506. DOI: https://doi.org/10.1096/fj.202000143RRR .
18. Wang H, Chen W, Li D, Yin X, Zhang X, Olsen N, Zheng SG. Vitamin D and Chronic Diseases. Aging Dis, 2017;8:346-53. DOI: https://doi.org/10.14336/AD.2016.1021.
19. Cantorna, Margheritta T, Lin YD, Yang L. Vitamin D and 1,25 (OH)2D regulation of T cells. Nutrients. 2015;7:3011-21. DOI: https://doi.org/10.3390/nu7043011.
20. Singh K, Coburn LA, Barry DP, Asim M, Scull BP, Allaman MM, Lewis ND Washington MK, Rosen MJ, Williams CS, Chaturvedi R, Wilson KT. Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis and leads to an IL-17-predominant T cell response. Am J Physiol Gastrointest Liver Physiol. 2013; 305: G225–G240. DOI: https://doi.org/10.1152/ajpgi.00091.2013.
21. He Y, Lin LJ, Zheng CQ, Jin Y, Lin Y. Cytokine expression and the role of Th17 cells in a mouse model of colitis. Molecular Medicine Report. 2012;6:1438-42. DOI: https://doi.org/10.3892/mmr.2012.1111.
22. Nobile S, Tenace MA, Pappa HM. The Role of Vitamin D in the Pathogenesis of Inflammatory Bowel Disease. Gastrointest Disord. 2019; 1: 231-40. DOI: https://doi.org/10.3390/gidisord1010018.
23. Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemical-induced in ammatory bowel disease models in rodents. Korean J Physiol Pharmacol. 2014;18:279-88. DOI: https://doi.org/10.4196/kjpp.2014.18.4.279.
24. Saleh MM, Frisbee AL, Leslie JL, Scully KW, Abhyankar MM, Petri WA. Colitis-induced Th17 cells increase the risk for severe subsequent clostridium difficile infection. Cell Host & Microbe. 2019;25:756-65.e5. DOI: https://doi.org/10.1016/j.chom.2019.03.003.
Published
2022-12-28
How to Cite
1.
Paramitha F, Wibowo S. Role of vitamin D3 on IL-17 expression in colon and improvement of colonic mucosa in an inflammatory bowel disease mice model. PI [Internet]. 28Dec.2022 [cited 20Jun.2024];63(1sup):1-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/3177
Section
Pediatric Gastrohepatology
Received 2022-09-27
Accepted 2022-12-28
Published 2022-12-28