EXPRESSION OF β-DEFENSIN-1 IN RAT COLON TISSUE

DOI: https://doi.org/10.29296/24999490-2019-06-09

E.Yu. Bystrova, O.N. Platonova, A.A. Shpanskaya, K.A. Dvornikova, A.D. Nozdrachev I.P. Pavlov Institute of Physiology, Makarova Emb., 6, Saint-Petersburg, 199034, Russian Federation E-mail: [email protected]

Introduction. At present, signaling pathways involved in the development of innate and adaptive immune responses and comprising, inter alia, the interaction of pattern-recognizing receptors, such as TLR, with antimicrobial peptides associated with inflammation, proliferation, production of cytokines and chemokines, are actively studied. Among them, there is β-defensin, the localization of which in rat colon tissue and expression changes under bacterial endotoxemia are still poorly understood. At the same time, an important problem in the study of neuroimmune interactions is to reveal potential relationships between the production of endogenous defensins and TLR expression, in particular, by enteric neurons. The aim of the study. In the present study, we investigated the localization of β-defensin-1 (rBD1) in rat colon tissue under normal conditions and on the model of bacterial endotoxemia induced by Escherichia coli lipopolysaccharide (LPS). Results. By means of immunohistochemistry, we have shown rBD1 to be mainly localized in the submucous layer of the rat colon and characterized by constitutive and inducible expression. Bacterial endotoxemia provides a statistically significant increase in rBD1 expression after 6 hours and 24 hours following LPS administration. Conclusion. Despite the lack of convincing data verifying the expression of β-defensin-1 by enteric neurons, we cannot exclude endogenous inducible defensins upregulation following LPS administration through signaling pathways associated with TLR4, which is expressed by rat colon sensory neurons.
Keywords: 
antimicrobial peptides, β-defensin-1, TLR4, enteric neurons
Список литературы: 
  1. Hazlett L., Wu M. Defensins in innate immunity. Cell Tissue Res. 2011; 343: 175–88. https://doi.org/10.1007/s00441-010-1022-4
  2. Patel S., Akhtar N. Antimicrobial peptides (AMPs): The quintessential ‘offense and defense’ molecules are more than antimicrobials. Biomedicine & Pharmacotherapy. 2017; 95: 1276–83. https://doi.org/10.1016/j.biopha.2017.09.042
  3. Fry D.E. Antimicrobial peptides. Surgical infections. 2018; 19 (8): 804–11. https://doi.org/10.1089/sur.2018.194
  4. Bals R. Epithelial antimicrobial peptides in host defense against infection. Respir. Res. 2000; 1: 141–50. https://doi.org/10.1186/rr25
  5. Mamchur V.I., Levyh A.E. Defenziny – endogennye peptidy s antiinfektsionnymi i protivoopuholevymi svojstvami. Tavricheskij mediko-biologicheskij vestnik. 2012; 15 (2): 315–21. [Mamchur V.I., Levyh A.E. Defensins – endogenous peptides with anti-infectious and anti-tumor properties. Tavricheskij mediko-biologicheskij vestnik. 2012; 15 (2): 315–21 (in Russian)]
  6. Avila E.E. Functions of antimicrobial peptides in vertebrates. Curr. Protein Pept. Sci. 2017; 18 (11): 1098–119. https://doi.org/10.2174/1389203717666160813162629
  7. Sankaran-Walters S., Hart R., Dills C. Guardians of the gut: enteric defensins. Frontiers in Microbiology. 2017; 8: 1–8. https://doi.org/10.3389/fmicb.2017.00647
  8. Yang D., Biragyn A., Kwak L.W., Oppenheim J.J. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 2002; 23 (6): 291–6. https://doi.org/10.1016/S1471-4906(02)02246-9
  9. Mattar E.H., Almehdar H.A., Yacoub H.A., Uversky V.N., Redwan E.M. Antimicrobial potentials and structural disorder of human and animal defensins. Cytokine & Growth Factor Reviews. 2016; 28: 95–111. https://doi.org/10.1016/j.cytogfr.2015.11.002
  10. Selsted M.E., Ouellette A.J. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 2005; 6 (6): 551–7. https://doi.org/10.1038/ni1206
  11. Nguyen T.X., Cole A.M., Lehrer R.I. Evolution of primate theta defensins: a serpentine path to a sweet tooth. Peptides. 2003; 24 (11): 1647–54. https://doi.org/10.1016/j.peptides.2003.07.023
  12. Vora P., Youdim A., Thomas L.S., Fukata M., Tesfay S.Y., Lukasek K., Michelsen K.S., Wada A., Hirayama T., Arditi M., Abreu M.T. β-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol. 2004; 173 (9): 5398–405. https://doi.org/10.4049/jimmunol.173.9.5398
  13. Gariboldi S., Palazzo M., Zanobbio L., Selleri S., Sommariva M., Sfondrini L., Cavicchini S., Balsari A., Rumio C. Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of β-defensin 2 via TLR2 and TLR4. J. Immunol. 2008; 181 (3): 2103–5405. https://doi.org/10.4049/jimmunol.181.3.2103
  14. Hill D.R., Kessler S.P., Rho H.K., Cowman M.K., de la Motte C.A. Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium. J. Biol. Chem. 2012; 287 (36): 30610–24. https://doi.org/10.1074/jbc.M112.356238
  15. Hill D.R., Rho H.K., Kessler S.P., Amin R., Homer C.R., McDonald C., Cowman M.K., de la Motte C.A. Human milk hyaluronan enhances innate defense of the intestinal epithelium. J. Biol. Chem. 2013; 288 (40): 29090–104. https://doi.org/10.1074/jbc.M113.468629
  16. Barajon I., Serrao G., Arnaboldi F., Opizzi E., Ripamonti G., Balsari A., Rumio C. Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J. Histochem. Cytochem. 2009; 57 (11): 1013–23. https://doi.org/10.1369/jhc.2009.953539
  17. 17. Filippova L.V., Malyshev F.S., Bykova A.A., Nozdrachev A.D. Ekspressija Toll-podobnyh retseptorov 4 v nervnyh spletenijah dvenadtsatiperstnoj, toschej i obodochnoj kishki krysy. Doklady Akademii nauk. 2012; 445 (3): 353–5. https://doi.org/10.1134/S0012496612040114 [Filippova L.V., Malyshev F.S., Bykova A.A., Nozdrachev A.D. Expression of Toll-like receptors 4 in the nerve plexuses of rat duodenum, jejunum and colon. Doklady Biological Sciences. 2012; 445 (3): 353–5 (in Russian)]
  18. Filippova L.V., Bystrova E.Ju., Malyshev F.S., Shpanskaja A.A., Nozdrachev A.D. Osobennosti lokalizatsii pattern-raspoznajuschih i vaniloidnyh retseptorov v nervnyh spletenijah kishki krysy. Doklady Akademii Nauk. 2013; 452 (3): 342–5. https://doi.org/10.1134/S0012496613050074 [Filippova L.V., Bystrova E.Yu., Malyshev F.S., Shpanskaya A.A., Nozdrachev A.D. Location of pattern-recognizing and vanilloid receptors in the nerve plexuses of rat intestine. Doklady Biological Sciences. 2013; 452 (3): 342–5 (in Russian)]
  19. Kozar R.A., Santora R.J., Poindexter B.J., Milner S.M., Bick R.J. Alterations in content and localization of defensins in rat ileum and jejunum following ischemia-reperfusion. Specific peptides, in specific places, for specific jobs? Open Access Journal of Plastic Surgery. 2011; 11: 58–69.
  20. Williams W.M., Torres S., Siedlak S.L., Castellani R.J., Perry G., Smith M.A., Zhu X. Antimicrobial peptide β-defensin-1 expression is upregulated in Alzheimer’s brain. J. of Neuroinflammation. 2013; 10 (127): 1–11. https://doi.org/10.1186/1742-2094-10-127