Gene expression of antimicrobial peptides in rat intestine under conditions of chronic stress
- Authors: Berezhnoy A.V.1, Yankelevich I.A.1, Aleshina G.M.1, Shamova O.1
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Affiliations:
- Institute of Experimental Medicine
- Section: Original research
- URL: https://journals.eco-vector.com/MAJ/article/view/623704
- DOI: https://doi.org/10.17816/MAJ623704
- ID: 623704
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Abstract
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, dysbiosis, inflammatory processes, functional dyspepsia, biliary dyskinesia, etc. 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 response of molecular factors of the innate immunity in intestine, such as antimicrobial peptides (AMP) secreted by intestinal epithelial cells upon infection, to the chronic stress. 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, using a model of daily repeated forced swimming in cold water. 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. 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
Alexey Viktorovich Berezhnoy
Institute of Experimental Medicine
Email: aleksey.berezhnoy@pharminnotech.com
ORCID iD: 0009-0007-0288-3643
Irina Alekseevna Yankelevich
Institute of Experimental Medicine
Email: irinkab@bk.ru
ORCID iD: 0000-0002-9982-1006
Galina Matveevna Aleshina
Institute of Experimental Medicine
Email: galina_aleshina@mail.ru
ORCID iD: 0000-0003-2886-7389
Olga Shamova
Institute of Experimental Medicine
Author for correspondence.
Email: oshamova@yandex.ru
ORCID iD: 0000-0002-5168-2801
Scopus Author ID: 6603643804
ResearcherId: F-6743-2013
Associate Professor, Dr. Sci. (Biol.), Corresponding Member of the Russian Academy of Sciences, Head of the Department of General Pathology and Pathological Physiology
Russian Federation, 197022, Санкт-Петербург, ул. академика Павлова, д. 12References
- 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
- 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
- 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
- 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
- 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
- Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Current opinion in gastroenterology. 2015; 31(1): 69-75. doi: 10.1097/MOG.0000000000000139
- 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
- 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
- Menees S, Chey W. The gut microbiome and irritable bowel syndrome. F1000Research. 2018; 7 (F1000 Faculty Rev):1029. doi: 10.12688/f1000research.14592.1
- Sapna Sharma, Prabhanshu Tripathi, Gut microbiome and type 2 diabetes: where we are and where to go? The Journal of Nutritional Biochemistry. 2019; 63:101-108, doi: 10.1016/j.jnutbio.2018.10.003.
- 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
- Kirby TO, Ochoa-Repáraz J. The Gut Microbiome in Multiple Sclerosis: A Potential Therapeutic Avenue. Medical sciences (Basel, Switzerland). 2018; 6(3):69. doi: 10.3390/medsci6030069
- Boziki MK, Kesidou E, Theotokis P, et al. Microbiome in Multiple Sclerosis; Where Are We, What We Know and Do Not Know. Brain sciences. 2020; 10(4): 234. doi: 10.3390/brainsci10040234
- 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 biology. 2020; 18(1):62. doi: 10.1186/s12915-020-00775-7
- Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34(46):15490-15496. doi: 10.1523/JNEUROSCI.3299-14.2014.
- Mukherjee S, Hooper LV. Antimicrobial Defense of the Intestine, Immunity. 2015; 42(1):28-39 doi: 10.1016/j.immuni.2014.12.028.
- Muniz LR, Knosp C, Yeretssian G. Intestinal antimicrobial peptides during homeostasis, infection, and disease. Frontiers in immunology. 2012; 3: 310. doi: 10.3389/fimmu.2012.00310
- Sankaran-Walters S, Hart R, Dills C. Guardians of the Gut Enteric Defensins. Frontiers in microbiology. 2017; 8: 647. doi: 10.3389/fmicb.2017.00647
- Schroeder BO, Ehmann D., Precht JC et al. Paneth cell α-defensin 6 (HD-6) is an antimicrobial peptide. Mucosal Immunol. 2015; 8:661-671. doi: 10.1038/mi.2014.100
- Wilson SS, Wiens ME, Holly MK, et al. Defensins at the Mucosal Surface: Latest Insights into Defensin-Virus Interactions. Journal of virology. 2016; 90(11):5216-5218. doi: 10.1128/JVI.00904-15
- Park MS, Kim JI, Lee I, et al. Towards the Application of Human Defensins as Antivirals. Biomolecules & therapeutics. 2018; 26(3):242-254. doi: 10.4062/biomolther.2017.172
- 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
- Agier J, Efenberger M, Brzezińska-Błaszczyk E. Cathelicidin impact on inflammatory cells. Central-European journal of immunology. 2015; 40(2):225-235. doi: 10.5114/ceji.2015.51359
- Yankelevich I.A., Filatenkova T.A., Shustov M.V. 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
- Gruver AL, Sempowski GD. Cytokines, leptin, and stress-induced thymic atrophy. Journal of leukocyte biology. 2008; 84(4):915-923. doi: 10.1189/jlb.0108025
- Bulgakova O.S., Barantseva V.I. General clinical blood analysis as a method for determining post-stress rehabilitation. Uspekhi sovremennogo estestvoznaniya. 2009; 6: 22-27. (in Russ.) https://natural-sciences.ru/ru/article/view?id=13887
- Kiseleva N.M., Kuzmenko L.G., Nkane Nzola M.M. Stress and lymphocytes // Pediatrics. The journal named after G.N. Speransky. 2012.;91(1):137-143. (in Russ.) https://cyberleninka.ru/article/n/stress-i-limfotsity
- 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
- Nishitani N, Sakakibara H. Association of Psychological Stress Response of Fatigue with White Blood Cell Count in Male Daytime Workers. Industrial Health. 2014; 52(6):531-534. doi: 10.2486/indhealth.2013-0045
- Mallampali RK, Wang G, Wiles K, Tack BF 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.
- 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. PMID: 20222124
- 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.
- 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.
- 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
- https://www.uniprot.org/uniprot/Q32ZI4
- Su KH, Dai C. mTORC1 senses stresses: Coupling stress to proteostasis. BioEssays : news and reviews in molecular, cellular and developmental biology. 2017; 39(5):10.1002/bies.201600268. doi: 10.1002/bies.201600268
- 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 Advances. 2020; 10(6): 3371-3379. doi: 10.1039/c9ra10477a
- Radek KA. Antimicrobial anxiety: the impact of stress on antimicrobial immunity. Journal of leukocyte biology. 2010; 88(2):263-277. doi: 10.1189/jlb.1109740
- Aberg KM, Radek KA, Choi EH. Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice. The Journal of clinical investigation. 2007; 117(11):3339-3349. doi: 10.1172/JCI31726.
- Sugi Y, Takahashi K, Kurihara K, et al. α-Defensin 5 gene expression is regulated by gut microbial metabolites. Bioscience, biotechnology, and biochemistry. 2017; 81(2):242-248. doi: 10.1080/09168451.2016.1246175