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Biochemistry (Moscow)

, Volume 81, Issue 11, pp 1303–1308 | Cite as

Microbiota induces expression of tumor necrosis factor in postnatal mouse skin

  • D. V. Yuzhakova
  • M. V. Shirmanova
  • A. A. Bocharov
  • I. V. Astrakhantseva
  • E. A. Vasilenko
  • E. N. Gorshkova
  • M. S. Drutskaya
  • E. V. Zagaynova
  • S. A. Nedospasov
  • A. A. KruglovEmail author
Molecular and Cellular Mechanisms of Inflammation (Special Issue) Guest Editors S. A. Nedospasov and D. V. Kuprash

Abstract

Tumor necrosis factor (TNF) is a pleiotropic cytokine that regulates many important processes in the body. TNF production in a physiological state supports the structure of lymphoid organs and determines the development of lymphoid cells in hematopoiesis. However, chronic TNF overexpression leads to the development of various autoimmune disorders. Sites of TNF production in the naive state remain unclear due to the lack of in vivo models. In the present study, we used TNF-2A-Kat reporter mice to monitor the expression of TNF in different tissues. Comparative analysis of tissue fluorescence in TNF-2A-Kat reporter mice and wild type mice revealed constitutive expression of TNF in the skin of naive adult mice. In the skin of TNF-2A-Kat reporter mouse embryos, no statistically significant differences in the expression of TNF compared to wild type animals were observed. Furthermore, we established that local depletion of microflora with topical antibiotics leads to a reduction in the fluorescence signal. Thus, we assume that the skin microflora is responsible for the expression of TNF in the skin of mice.

Keywords

tumor necrosis factor (TNF) TNF-2A-Kat reporter mice in vivo fluorescent imaging 

Abbreviations

AMP

antimicrobial peptides

IFN

interferon

IL

interleukin

TNF

tumor necrosis factor

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References

  1. 1.
    Belkaid, Y., and Tamoutounour, S. (2016) The influence of skin microorganisms on cutaneous immunity, Nat. Rev. Immunol., 16, 353–366.CrossRefPubMedGoogle Scholar
  2. 2.
    Grice, E. A., and Segre, J. A. (2011) The skin microbiome, Nat. Rev. Microbiol., 9, 244–253.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Borkowski, A. W., and Gallo, R. L. (2011) The coordinated response of the physical and antimicrobial peptide barriers of the skin, J. Invest. Dermatol., 131, 285–287.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kruglov, A. A., Tumanov, A. V., Grivennikov, S. I., Shebzukhov, Y. V., Kuchmiy, A. A., Efimov, G. A., Drutskaya, M. S., Scheller, J., Kuprash, D. V., and Nedospasov, S. A. (2011) Modalities of experimental TNF blockade in vivo: mouse models, Adv. Exp. Med. Biol., 691, 421–431.CrossRefPubMedGoogle Scholar
  5. 5.
    Taylor, P. C., and Feldmann, M. (2009) Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis, Nat. Rev. Rheumatol., 5, 578–582.CrossRefPubMedGoogle Scholar
  6. 6.
    Fierer, N., Hamady, M., Lauber, C. L., and Knight, R. (2008) The influence of sex, handedness, and washing on the diversity of hand surface bacteria, Proc. Natl. Acad. Sci. USA, 105, 17994–17999.CrossRefPubMedGoogle Scholar
  7. 7.
    Bashan, A., Gibson, T. E., Friedman, J., Carey, V. J., Weiss, S. T., Hohmann, E. L., and Liu, Y. Y. (2016) Universality of human microbial dynamics, Nature, 534, 259–262.CrossRefPubMedGoogle Scholar
  8. 8.
    Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., and Relman, D. A. (2005) Diversity of the human intestinal microbial flora, Science, 308, 1635–1638.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Dewhirst, F. E., Chen, T., Izard, J., Paster, B. J., Tanner, A. C., Yu, W. H., Lakshmanan, A., and Wade, W. G. (2010) The human oral microbiome, J. Bacteriol., 192, 5002–5017.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zaura, E., Keijser, B. J., Huse, S. M., and Crielaard, W. (2009) Defining the healthy “core microbiome” of oral microbial communities, BMC Microbiol., 9, 259.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bik, E. M., Long, C. D., Armitage, G. C., Loomer, P., Emerson, J., Mongodin, E. F., Nelson, K. E., Gill, S. R., Fraser-Liggett, C. M., and Relman, D. A. (2010) Bacterial diversity in the oral cavity of 10 healthy individuals, ISME J., 4, 962–974.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bik, E. M., Eckburg, P. B., Gill, S. R., Nelson, K. E., Purdom, E. A., Francois, F., Perez-Perez, G., Blaser, M. J., and Relman, D. A. (2006) Molecular analysis of the bacterial microbiota in the human stomach, Proc. Natl. Acad. Sci. USA, 103, 732–737.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Pei, Z. H., Bini, E. J., Yang, L. Y., Zhou, M. S., Francois, F., and Blaser, M. J. (2004) Bacterial biota in the human distal esophagus, Proc. Natl. Acad. Sci. USA, 101, 4250–4255.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Gao, Z., Tseng, C. H., Pei, Z., and Blaser, M. J. (2007) Molecular analysis of human forearm superficial skin bacterial biota, Proc. Natl. Acad. Sci. USA, 104, 2927–2932.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Grice, E. A., Kong, H. H., Renaud, G., Young, A. C., Bouffard, G. G., Blakesley, R. W., Wolfsberg, T. G., Turner, M. L., and Segre, J. A. (2008) A diversity profile of the human skin microbiota, Genome Res., 18, 1043–1050.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Costello, E. K., Lauber, C. L., Hamady, M., Fierer, N., Gordon, J. I., and Knight, R. (2009) Bacterial community variation in human body habitats across space and time, Science, 326, 1694–1697.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Braff, M. H., Bardan, A., Nizet, V., and Gallo, R. L. (2005) Cutaneous defense mechanisms by antimicrobial peptides, J. Invest. Dermatol., 125, 9–13.CrossRefPubMedGoogle Scholar
  18. 18.
    Massoud, T. F., and Gambhir, S. S. (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light, Genes Dev., 17, 545–580.CrossRefPubMedGoogle Scholar
  19. 19.
    Germain, R. N., Miller, M. J., Dustin, M. L., and Nussenzweig, M. C. (2006) Dynamic imaging of the immune system: progress, pitfalls and promise, Nat. Rev. Immunol., 6, 497–507.CrossRefPubMedGoogle Scholar
  20. 20.
    Shebzukhov, Y. V., Kuchmiy, A. A., Kruglov, A. A., Zipp, F., Siffrin, V., and Nedospasov, S. A. (2014) Experimental applications of TNF-reporter mice with far-red fluorescent label, Methods Mol. Biol., 1155, 151–162.CrossRefPubMedGoogle Scholar
  21. 21.
    Luker, G. D., and Luker, K. E. (2008) Optical imaging: current applications and future directions, J. Nucl. Med., 49, 1–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Kuchmiy, A. A., Efimov, G. A., and Nedospasov, S. A. (2012) Methods for in vivo molecular imaging, Biochemistry (Moscow), 77, 1339–1353.CrossRefGoogle Scholar
  23. 23.
    Chudakov, D. M., Matz, M. V., Lukyanov, S., and Lukyanov, K. A. (2010) Fluorescent proteins and their applications in imaging living cells and tissues, Physiol. Rev., 90, 1103–1163.CrossRefPubMedGoogle Scholar
  24. 24.
    Chudakov, D. M., Belousov, V. V., Zaraisky, A. G., Novoselov, V. V., Staroverov, D. B., Zorov, D. B., Lukyanov, S., and Lukyanov, K. A. (2003) Kindling fluorescent proteins for precise in vivo photolabeling, Nat. Biotechnol., 21, 191–194.CrossRefPubMedGoogle Scholar
  25. 25.
    Stoll, S., Delon, J., Brotz, T. M., and Germain, R. N. (2002) Dynamic imaging of T cell-dendritic cell interactions in lymph nodes, Science, 296, 1873–1876.CrossRefPubMedGoogle Scholar
  26. 26.
    Mempel, T. R., Henrickson, S. E., and Von Andrian, U. H. (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases, Nature, 427, 154–159.CrossRefPubMedGoogle Scholar
  27. 27.
    Bousso, P., Bhakta, N. R., Lewis, R. S., and Robey, E. (2002) Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy, Science, 296, 1876–1880.CrossRefPubMedGoogle Scholar
  28. 28.
    Kumar, S., Skeen, M. J., Adiri, Y., Yoon, H., Vezys, V. D., Lukacher, A. E., Evavold, B. D., Ziegler, H. K., and Boss, J. M. (2005) A cytokine promoter/yellow fluorescent protein reporter transgene serves as an early activation marker of lymphocyte subsets, Cell Immunol., 237, 131140.CrossRefGoogle Scholar
  29. 29.
    Stetson, D. B., Mohrs, M., Reinhardt, R. L., Baron, J. L., Wang, Z. E., Gapin, L., Kronenberg, M., and Locksley, R. M. (2003) Constitutive cytokine mRNAs mark natural killer (NK) and NKT-cells poised for rapid effector function, J. Exp. Med., 198, 1069–1076.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kravchenko, V. V., Kaufmann, G. F., Mathison, J. C., Scott, D. A., Katz, A. Z., Grauer, D. C., Lehmann, M., Meijler, M. M., Janda, K. D., and Ulevitch, R. J. (2008) Modulation of gene expression via disruption of NFkappaB signaling by a bacterial small molecule, Science, 321, 259–263.CrossRefPubMedGoogle Scholar
  31. 31.
    Kuchmiy, A. A., Kruglov, A. A., Galimov, A. R., Shebzukhov, Yu. V., Chudakov, D. M., Lukyanov, S. A., and Nedospasov, S. A (2011) New line of transgenic reporter mice for studying the expression of tumor necrosis factor, Russ. Immunol. J., 5, 205–214.Google Scholar
  32. 32.
    Tracey, D., Klareskog, L., Sasso, E. H., Salfeld, J. G., and Tak, P. P. (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review, Pharmacol. Ther., 117, 244–279.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • D. V. Yuzhakova
    • 1
    • 2
  • M. V. Shirmanova
    • 1
  • A. A. Bocharov
    • 3
  • I. V. Astrakhantseva
    • 2
  • E. A. Vasilenko
    • 2
  • E. N. Gorshkova
    • 2
  • M. S. Drutskaya
    • 3
  • E. V. Zagaynova
    • 1
  • S. A. Nedospasov
    • 2
    • 3
    • 4
    • 5
  • A. A. Kruglov
    • 2
    • 4
    • 5
    Email author
  1. 1.Nizhny Novgorod State Medical AcademyNizhny NovgorodRussia
  2. 2.Lobachevsky State University of Nizhny NovgorodNizhny NovgorodRussia
  3. 3.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia
  4. 4.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  5. 5.Faculty of BiologyLomonosov Moscow State UniversityMoscowRussia

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