CHANGES OF mRNA GENE EXPRESSION LEVEL OF AIRE, DEAF1, FOXP3, CTLA4 AND IL-10 IN THE OFFSPRING OF RATS WITH EXPERIMENTAL GESTATIONAL DIABETES AND IN CONDITIONS OF INSULIN ORAL TOLERANCE FORMATION
DOI:
https://doi.org/10.21856/j-PEP.2016.3.06Keywords:
experimental gestational diabetes, mesenteric lymph nodes, Aire, Deaf1, FoxpAbstract
Using molecular genetic and immunofluorescence techniques it was investigated the mRNA gene expression level of Aire, Deaf1, Foxp3, Ctla4 and Il-10 in the offspring of rats with experimental gestational diabetes and in conditions of insulin oral tolerance formation. To determine the level of mRNA it was studied gene RT-PCR and was performed in real time thermocycler CFX96 ™ RealTime PCR Detection Systems («Bio-Rad Laboratories, Inc.», USA). It was observed such violations of immunotolerance: AIRE gene repression, reduced mRNA levels of Deaf1 and the transcription factor Foxp3. Numbers of T-regulatory cells were decreased, which was confirmed by inhibition of gene expression cytokine Il-10 and the negative Ctla4 costimulatory molecule. Oral injection of insulin during first 2 weeks compensated these changes. It caused transcriptional activation of the gene AIRE, Deaf1, Foxp3, Ctla4 and Il-10, increased the number of Foxp3+ cells in mesenteric lymph nodes.
References
Metzger T, Anderson M. Immunol Rev 2011; 241(1):89-103.
Kojima H, Fujimiya M, Matsumura K, et al. Proc Natl Acad Sci USA 2004; 101:2458-2463.
Cohen J, Tewalt E, Rouhani S. PLoS ONE 2014; 9(2):doi: http://doi.org/10.1371/journal.pone.0087740.
Yip L, Su L, Sheng D, et al. Nat Immunol 2009; 10:1026-1033.
Shevach E, Thornton A. Immunol Rev 2014; 259(1):88-102.
Wang S, Gao X, Shen G, et al. Sci Rep 2016:doi: http://doi.org/10.1038/srep24249.
Walker LS, Sansom DM. Trends Immunol 2015; 36(2):63-70.
Hammerschmidt S, Ahrendt M, Bode U, et al. J Exp Med 2008; 205:2483-2490.
Yang S, Fujikado N, Kolodin D, et al. Science 2015; 348(6234):589-594.
Macpherson A, Smith K. J Exp Med 2006; 203(3):497-500.
Kunkel D, Kirchhoff D, Nishikawa S, et al. Eur J Immunol 2003; 33:1292-1301.
Spahn TW, Weiner HL, Rennert PD, et al. Eur J Immunol 2002; 32:1109-1113.
Huang FP, Platt N, Wykes M, et al. J Exp Med 2000; 191:435-444.
Worbs T, Boke U., Yan S, et al. J Exp Med 2006; 203:519-527.
Roep BO, Tree TI. Nat Rev Endocrinol 2014:10:229-242.
Gale EA, Emmett PJ, Collier CL, et al. Lancet 2004; 363:925-931.
Bonifacio E, Ziegler AG, Klingensmith G, et al. JAMA 2015; 313(15):1541-1549.
Roep BO. Nat Rev Endocrinology 2015; 11:451-452.
Zhang J, Davidson L, Eisenbarth G, et al. Proc Natl Acad Sci USA 1991; 88:10252-10256.
Kamyshny A, Putilin D, Kamyshna V. Mediterranean J Biosci 2015; 1(1):20-26.
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