Gene expression of antimicrobial peptides in rat intestine under conditions of chronic stress

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Abstract

BACKGROUND: Severe stress causes an array of dysfunctions in the immune, neuroendocrine, cardiovascular, digestive and other systems, resulting in an emergence of various types of pathology. Common manifestations of a chronic stress are the disorders in the gastrointestinal tract, such as irritable bowel syndrome, functional dyspepsia, biliary dyskinesia, dysbiosis, inflammatory processes that determine the development of gastritis and one of the most widespread post-stress pathologies of the gastrointestinal tract — stomach ulcers. The disclosure of the molecular mechanisms of a pathogenesis of diseases associated with gastrointestinal dysfunction related to chronic stress as well as a search for new ways to correct these disorders are important tasks of fundamental and clinical medicine. The present work is focused on evaluating a participation of molecular factors of the innate immunity in intestine, such as antimicrobial peptides secreted by intestinal epithelial cells upon infection, in a response to the chronic stress.

AIM: The aim of the study was to estimate the gene expression of a number of antimicrobial peptides: intestinal α- and β-defensins of laboratory animals (rats) under chronic stress conditions.

MATERIALS AND METHODS: Modeling of a chronic stress was performed by daily forced swimming of laboratory animals in cold water. An expression of α- and β-defensin genes was evaluated using a real-time polymerase chain reaction.

RESULTS: We found an increase in the level of expression of the rat α-defensin-5 and β-defensin-3 genes in response to chronic stress, while the expression of β-defensin-2 gene was not changed compared to the control.

CONCLUSIONS: Considering that changes in the concentration and spectrum of peptides with antibacterial activity, caused by prolonged stress, can contribute to modification of the composition of the intestinal microbiota, the data obtained can expand our understanding of the molecular basis of the pathogenesis of diseases associated with disorders in the composition of microbiota under stress.

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About the authors

Aleksei V. Berezhnoy

Institute of Experimental Medicine

Email: aleksey.berezhnoy@pharminnotech.com
ORCID iD: 0009-0007-0288-3643

PhD student

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Irina A. Yankelevich

Institute of Experimental Medicine

Email: irinkab@bk.ru
ORCID iD: 0000-0002-9982-1006
SPIN-code: 9249-6844

Cand. Sci. (Biol.), Senior Research Associate

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Galina M. Aleshina

Institute of Experimental Medicine

Email: galina_aleshina@mail.ru
ORCID iD: 0000-0003-2886-7389
SPIN-code: 4479-0630

Dr. Sci. (Biol.), Assistant Professor, Head of a Laboratory

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Olga V. Shamova

Institute of Experimental MedicineInstitute of Experimental Medicine

Author for correspondence.
Email: oshamova@yandex.ru
ORCID iD: 0000-0002-5168-2801
SPIN-code: 2913-4726
Scopus Author ID: 6603643804
ResearcherId: F-6743-2013

Dr. Sci. (Biol.), Corresponding Member of RAS, Head of a Department

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

References

  1. Ouellette AJ. Defensin-mediated innate immunity in the small intestine. Best Pract Res Clin Gastroenterol. 2004;18:405–419. doi: 10.1016/j.bpg.2003.10.010
  2. Wehkamp J, Wang G, Kübler I, et al. The Paneth cell alpha-defensin deficiency of ileal Crohn’s disease is linked to Wnt/Tcf-4. J. Immunol. 2007;179:3109–3118. doi: 10.4049/jimmunol.179.5.3109
  3. Wilson CL, Ouellette AJ, Satchell DP, et al. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science. 1999;286:113–117. doi: 10.1126/science.286.5437.113
  4. Salzman NH, Ghosh D, Huttner KM, et al. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature. 2003;422:522–526. doi: 10.1038/nature01520
  5. Young VB. The role of the microbiome in human health and disease: an introduction for clinicians. BMJ. 2017;356:j831. doi: 10.1136/bmj.j831
  6. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31(1):69–75. doi: 10.1097/MOG.0000000000000139
  7. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:k2179. doi: 10.1136/bmj.k2179
  8. Pittayanon R, Lau JT, Yuan Y, et al. Gut microbiota in patients with irritable bowel syndrome – a systematic review. Gastroenterology. 2019;157(1):97–108. doi: 10.1053/j.gastro.2019.03.049
  9. Menees S, Chey W. The gut microbiome and irritable bowel syndrome. F1000Res. 2018;7:F1000 Faculty Rev-1029. doi: 10.12688/f1000research.14592.1
  10. Sharma S, Tripathi P. Gut microbiome and type 2 diabetes: where we are and where to go? J Nutr Biochem. 2019;63:101–108. doi: 10.1016/j.jnutbio.2018.10.003
  11. Das T, Jayasudha R, Chakravarthy S, et al. Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy. Sci Rep. 2021;11(1):2738. doi: 10.1038/s41598-021-82538-0
  12. Kirby TO, Ochoa-Repáraz J. The gut microbiome in multiple sclerosis: a potential therapeutic avenue. Med Sci (Basel, Switzerland). 2018;6(3):69. doi: 10.3390/medsci6030069
  13. Boziki MK, Kesidou E, Theotokis P, et al. Microbiome in multiple sclerosis; Where are we, what we know and do not know. Brain Sci. 2020;10(4):234. doi: 10.3390/brainsci10040234
  14. Baldini F, Hertel J, Sandt E, et al. Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC Biol. 2020;18(1):62. doi: 10.1186/s12915-020-00775-7
  15. Mayer EA, Knight R, Mazmanian SK, et al. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34(46):15490–15496. doi: 10.1523/JNEUROSCI.3299-14.2014
  16. Mukherjee S, Hooper LV. Antimicrobial defense of the intestine. Immunity. 2015;42(1):28–39. doi: 10.1016/j.immuni.2014.12.028
  17. Muniz LR, Knosp C, Yeretssian G. Intestinal antimicrobial peptides during homeostasis, infection, and disease. Front Immunol. 2012;3:310. doi: 10.3389/fimmu.2012.00310
  18. Sankaran-Walters S, Hart R, Dills C. Guardians of the gut enteric defensins. Front Microbiol. 2017;8:647. doi: 10.3389/fmicb.2017.00647
  19. Schroeder BO, Ehmann D, Precht JC, et al. Paneth cell α-defensin 6 (HD-6) is an antimicrobial peptide. Mucosal Immunol. 2015;8(3):661–671. doi: 10.1038/mi.2014.100
  20. Wilson SS, Wiens ME, Holly MK, et al. Defensins at the mucosal surface: latest insights into defensin-virus interactions. J Virol. 2016;90(11):5216–5218. doi: 10.1128/JVI.00904-15
  21. Park MS, Kim JI, Lee I, et al. Towards the application of human defensins as antivirals. Biomol Ther (Seoul). 2018;26(3):242–254. doi: 10.4062/biomolther.2017.172
  22. Harvey L, Kohlgraf K, Mehalick L, et al. Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus. Sci Rep. 2013;3:1232. doi: 10.1038/srep01232
  23. Agier J, Efenberger M, Brzezińska-Błaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol. 2015;40(2):225–235. doi: 10.5114/ceji.2015.51359
  24. Yankelevich IA, Filatenkova TA, Shustov MV. The effect of chronic emotional and chronic stress on the indicators of neuroendocrine and immune systems. Medical Academic Journal. 2019;19(1):85–90. (In Russ.) doi: 10.17816/MAJ19185-90
  25. Gruver AL, Sempowski GD. Cytokines, leptin, and stress-induced thymic atrophy. J Leukoc Biol. 2008;84(4):915–923. doi: 10.1189/jlb.0108025
  26. Bulgakova OS, Barantseva VI. General clinical blood analysis as a method for determining post-stress rehabilitation. Advances in current natural sciences. 2009;6:22–27. (In Russ.)
  27. Kiseleva NM, Kuzmenko LG, Nkane Nzola MM. Stress and lymphocytes. Pediatrics. The journal named after G.N. Speransky. 2012;91(1):137–143. (In Russ.)
  28. Swan MP, Hickman DL. Evaluation of the neutrophil-lymphocyte ratio as a measure of distress in rats. Lab Animal. 2014;43:276–282. doi: 10.1038/laban.529
  29. Nishitani N, Sakakibara H. Association of psychological stress response of fatigue with white blood cell count in male daytime workers. Ind Health. 2014;52(6):531–534. doi: 10.2486/indhealth.2013-0045
  30. Mallampali RK, Wang G, Wiles K, et al. Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins. Infect Immun. 1999;67(9):4827–4833. doi: 10.1128/IAI.67.9.4827-4833.1999
  31. Inaba Y, Ashida T, Ito T, et al. Expression of the antimicrobial peptide alpha-defensin/cryptdins in intestinal crypts decreases at the initial phase of intestinal inflammation in a model of inflammatory bowel disease, IL-10-deficient mice. Inflamm Bowel Dis. 2010;16(9):1488–1495. doi: 10.1002/ibd.21253
  32. Mathew B, Nagaraj R. Antimicrobial activity of human α-defensin 5 and its linear analogs: N-terminal fatty acylation results in enhanced antimicrobial activity of the linear analogs. Peptides. 2015;71:128–140. doi: 10.1016/j.peptides.2015.07.009
  33. Aoki-Yoshida A, Aoki R, Moriya N, et al. Omics studies of the murine intestinal ecosystem exposed to subchronic and mild social defeat stress. J Proteome Res. 2016;15(9):3126–3138. doi: 10.1021/acs.jproteome.6b00262
  34. Estienne M, Claustre J, Clain-Gardechaux G, et al. Maternal deprivation alters epithelial secretory cell lineages in rat duodenum: role of CRF-related peptides. Gut. 2010;59:744–751. doi: 10.1136/gut.2009.190728
  35. uniprot.org [Internet]. Q32ZI4 · DEFB3_RAT. Available from: https://www.uniprot.org/uniprot/Q32ZI4. Accessed: 22.11.2023.
  36. Su KH, Dai C. mTORC1 senses stresses: Coupling stress to proteostasis. Bioessays. 2017;39(5):10.1002/bies.201600268. doi: 10.1002/bies.201600268
  37. Tang Z, Shi B, Sun W, et al. Tryptophan promoted β-defensin-2 expression via the mTOR pathway and its metabolites: kynurenine banding to aryl hydrocarbon receptor in rat intestine. RSC Adv. 2020;10(6):3371–3379. doi: 10.1039/c9ra10477a
  38. Radek KA. Antimicrobial anxiety: the impact of stress on antimicrobial immunity. J Leukoc Biol. 2010;88(2):263–277. doi: 10.1189/jlb.1109740
  39. Aberg KM, Radek KA, Choi EH. Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice. J Clin Invest. 2007;117(11):3339–3349. doi: 10.1172/JCI31726
  40. Sugi Y, Takahashi K, Kurihara K, et al. α-Defensin 5 gene expression is regulated by gut microbial metabolites. Biosci Biotech Biochem. 2017;81(2):242–248. doi: 10.1080/09168451.2016.1246175

Supplementary files

Supplementary Files
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2. Fig. 1. Thymus mass (a) and the percentage of neutrophils in blood (b) of laboratory rats of the experimental group (стресс) exposed to chronic stress and in intact animals (контроль). *D ifferences with the control group are significant, Mann– Whitney U-test (p < 0.05), n = 8

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