EXPERIMENTAL GESTATIONAL DIABETES DISRUPTS THE FORMATION OF IMMUNE TOLERANCE IN OFFSPRING

The aim: To analyze the mRNA gene expression level of Aire, Deaf1, Foxp3, Ctla4, Il10, Nlrp3 and distribution of NLRP3+-cells in mesenteric lymph nodes (MLNs) of the offspring of rats with GD, both untreated and treated with glibenclamide and in conditions of insulin oral tolerance formation. Materi...

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Published in:	Wiadomości lekarskie (1960) Vol. 76; no. 1; p. 115
Main Authors:	Prozorova, Tatyana M, Zhulkevych, Igor V, Andreychyn, Serhiy M, Korylchuk, Neonila I, Hanberher, Irina I, Riabokon, Svitlana S, Kamyshnyi, Aleksander M
Format:	Journal Article
Language:	English
Published:	Poland 2023
Subjects:	Animals CTLA-4 Antigen Diabetes Mellitus, Experimental Diabetes, Gestational DNA-Binding Proteins Female Forkhead Transcription Factors Glyburide Humans Immune Tolerance Male NLR Family, Pyrin Domain-Containing 3 Protein Pregnancy Rats Transcription Factors experimental gestational diabetes insulin mesenteric lymph nodes NLRP3 - inflammasome glibenclamide gene expression
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Summary:	The aim: To analyze the mRNA gene expression level of Aire, Deaf1, Foxp3, Ctla4, Il10, Nlrp3 and distribution of NLRP3+-cells in mesenteric lymph nodes (MLNs) of the offspring of rats with GD, both untreated and treated with glibenclamide and in conditions of insulin oral tolerance formation. Materials and methods: The study involves 160 male rats, one- or six-month-old. The mRNA genes expression was studied by real time quantitative poly¬merase chain reaction. Structure of Nlrp3+ -cells population was studied by histological sections of MLNs. Results: We observed AIRE gene repression, reduced mRNA levels of Deaf1 and the transcription factor Foxp3 in offspring of rats with GD. This was accompanied by inhibition of IL-10 gene expression and negative costimulatory molecules Ctla4. The development of the experimental GD was accompanied by transcrip¬tional induction of the Nlrp3 gene in MLNs of descendants. The administration of glibenclamide to pregnant female rats with GD inhibited the transcription of the Nlrp3 gene only in one-month-old offspring (5.3-fold) and did not change it in six-month-old animals. In offspring of rats with GD, the density of the NLRP3+-lymphocyte population in the MLNs increased, more pronounced in one-month-old animals. The administration of glibenclamide to pregnant rats with GD reduced the number of NLRP3+ -lymphocytes only in one-month-old offspring (by 33.0 %), whereas this index in six month-old offspring even increased. Conclusions: Experimental prenatal hyperglycemia leads to increased proinflammatory signaling and violation of peripheral immunological tolerance formation more pronounced at one month of life.
ISSN:	0043-5147
DOI:	10.36740/WLek202301116