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Activity of reproductive steroidal hormones on the activation of indoleamine 2,3 dioxygenase - IDO - in cells present in the microenvironment of the mammary carcinoma of female dogs

Grant number: 15/20762-8
Support type:Regular Research Grants
Duration: June 01, 2016 - May 31, 2018
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:José Roberto Kfoury Júnior
Grantee:José Roberto Kfoury Júnior
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The enzyme indoleamine 2,3 dioxygenase - IDO plays an important role on the immune system regulation, impairing the development of an immune response in the microenvironment it is expressed. Its activation leads to tryptophan catabolism consequently depriving it to proliferating cells along with metabolites generation that induce these cells to apoptosis. It is known that steroidal reproductive hormones as estrogen and progesterone are capable of alter important immune cell functions including altering IDO expression, although the mechanisms involved are still unclear. Tumor cells and nearby are known for expressing IDO and to be sensitive to the referred hormones. Mammary carcinomas are one of the most common tumors in dogs and express IDO. Considering this context, this project aims to investigate the influence of estrogen and progesterone on IDO expression of cultured mammary carcinoma cells from bitches, focusing on clarifying potential mechanisms involved. Mammary carcinoma cells from bitches will be cultured and treated with estrogen or progesterone and their respective receptor antagonists, tamoxifen and mifepristone. Flow cytometry and quantitative western blotting will be conducted to evaluate IDO expression while mRNA will be measured by Real Time PCR. The expected results may confirm the influence of these hormones on IDO expression, as well as to suggest putative mechanisms involved in the process that would allow the enzyme modulation, favoring the development of therapeutic protocols in physiological or pathological conditions that require immune cells response. (AU)