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Proteasomes on thyroid tissue allotransplantation under induction of donor-specific tolerance in rats

Abstract

Proteasomes in the liver of August rats (RT1c) were investigated 30 days after allotransplantation of Wistar rat (RT1u) thyroid tissue under renal capsule with/without induction of donor-specific tolerance by donor splenocyte intraportal administration. The levels of total proteasome pool, immune proteasomes containing subunits LMP2 and/or LMP7, and proteasome regulators 19S and 11S were defined. Intact and sham-operated August rats were used as control groups. The level of all immune proteasome forms and 11S regulator increased while the level of the total proteasome pool and 19S regulator decreased in the liver of experimental animals compared to the control groups, which indicated changes of liver functional state after transplantation. The 19S/11S ratio increased in the liver of nontolerant rats compared to tolerant animals. In the liver of tolerant rats with accepted grafts, the number of mononuclear cells expressing the immune subunit LMP2 greatly increased in comparison with control and nontolerant animals. Study of accepted grafts showed an increase in the ratio of LMP2/LMP7 immune subunits and 19S/11S regulators in them, compared to the tissue replacing the rejected grafts. Immune proteasomes were almost completely absent from the control intact thyroid tissue, while 19S/11S ratio was maximal in it. Thus, the development of the immune reaction or its suppression are accompanied by a change in the balance between different proteasome forms. Immune subunit LMP7 and 11S regulator are associated with the response against donor tissue. On the contrary, immune subunit LMP2 and 19S regulator are likely to be important for the development of immune tolerance and surviving tissue functioning. Immunofluorescence assay revealed a low content of the immune proteasomes in the follicle cells. Probably, formation of antigens for the major histocompatibility complex class I molecules was impaired by the low content of immune proteasomes, which led to immunological tolerance of hormone-producing follicle cells.

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Abbreviations

DST:

donor-specific tolerance

MHC:

major histocompatibility complex

IFN:

interferon

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Correspondence to A. A. Stepanova.

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Original Russian Text © A.A. Stepanova, Ya.D. Karpova, G.A. Bozhok, V.D. Ustichenko, Yu.V. Lyupina, E.I. Legach, M.S. Vagida, D.B. Kazansky, T.P. Bondarenko, N.P. Sharova, 2014, published in Bioorganicheskaya Khimiya, 2014, Vol. 40, No. 1, pp. 42–54.

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Stepanova, A.A., Karpova, Y.D., Bozhok, G.A. et al. Proteasomes on thyroid tissue allotransplantation under induction of donor-specific tolerance in rats. Russ J Bioorg Chem 40, 36–47 (2014). https://doi.org/10.1134/S1068162014010105

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Keywords

  • proteasomes
  • immune proteasomes
  • portal tolerance
  • thyroid tissue transplantation
  • liver
  • immunological tolerance