Prosopis strombulifera induced immunomodulation improves type I diabetes progression in NOD mice.

PERSIA FA; HAPON MB; MACKERN-OBERTI JP; ABBA R; GAMARRA LUQUES C

Mendoza

Congreso; XXXVI Reunion Anual de la Sociedad de Biologia de Cuyo.; 2018

Sociedad de Biologia de Cuyo

Prosopis strombulifera (Lam.) Benth. (PS) is a native plant from Mendoza ? Argentina used regionally as antibiotic, astringent and analgesic agent. Recent studies of our laboratory demonstrate the PS activity against immunocompetent cells. On in vitro assays with murine splenocytes and sorted T cells, we found that PS inhibits splenocytes, CD4+ T and CD8+ cell activation when were stimulated with Concanavalin A (ConA), A23187 and anti-CD3/CD28 agonist monoclonal antibodies. In addition, PS decreases IFN-ã release by splenocytes after polyclonal activation with ConA; and reduces cellular proliferation measured by CFSE dilution. Alltogether, our previous results demonstrate that PS attenuates T cell activation, immune-related cytokines release and cellular proliferation. To validate these results, the goal of the present work is to confirm in vivo the immunomodulatory effects of PS. NOD (Non Obese Diabetic) mice is a common used animal model in Type I diabetes (TID) research and, characteristically, the animals develop TID mediated by cellular immune destruction of pancreatic beta-islets. By the use of this animal model, we hypothesized that oral administration of 150mg/animal/day (maximum no toxic tolerated dose) of PS will interfere with diabetes progression. In our experimental design, 2 groups of 10 NODs each were separated. Treated group, receive PS in drinking water at the mentioned doses and glycaemia was determined weekly for 10 weeks. Then, animals were euthanized and the pancreas were processed for histological evaluation of insulitis and the spleens were obtained for Rt-qPCR determination of granzymes and perforin expression. Our results evidenced that, after 10 weeks, PS treated animal group showed a significant reduction in glucose blood levels (Student T Test, p˂0.05) and, the microscopic quantification of insulitis, demonstrate a notorious diminution in lymphocytes infiltration of beta-islets acini in treated animals. The mRNA expression of granzymes and perforin were also quantified, and resulted significantly reduced. In conclusion, the obtained results confirm the bioavailabitlity of PS derived compounds, which are able to improve the TID progression by interfering with the autoimmune process. The presented data open a new research field destined to describe and characterize the immunomodulatory effects induced by PS.