Study of the immunomodulatory potential of Dehydroepiandrosterone (DHEA) in experimental intestinal inflammation

• Grant number: 12/17265-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2012
• Effective date (End): September 30, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Cristina Ribeiro de Barros Cardoso
• Grantee: Vanessa Beatriz Freitas Alves
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 10/20162-7 - The role of hypothalamus-pituitary-adrenal (HPA) axis and exogenous glucocorticoids in the modulation of immune response in inflammatory bowel disease, AP.JP

Abstract

IBD is considered a multifactorial disease that involves genetic susceptibility, environmental factors and the immune system. In IBD immunopathogenesis there is a dysfunction in the regulation of the immune system with exacerbated production of pro-inflammatory responses of Th1 and Th17 pattern (in Crohn's Disease, CD) in contrast to a reduction in the number or function of regulatory T cells (Tregs). Inflammatory immune responses can be modulated by the hypothalamic-pituitary-adrenal (HPA) axis through neuroimmunoendocrine interactions and cortisol secretion which, along with dehydroepiandrosterone (DHEA) may be produced by the adrenal glands. DHEA has been described as an important modulator of the immune response, but the precise mechanisms that relate the actions of this hormone with protection or susceptibility to IBD are not completely known yet. Thus, this project aims to understand the immunomodulatory role of DHEA in experimentally induced intestinal inflammation. Therefore, C57BL/6 mice will be submitted to the administration of water containing DSS (experimental model of colitis with immune response similar to CD) and will be treated or not with DHEA. The disease development will be assessed through clinical and histological parameters. In addition to characterize the inflammatory cells with emphasis on subpopulations of Th1, Treg and Th17 cells, we aim to evaluate the production of cytokines involved in the modulation of immune response in the development of colitis in animals treated or not with DHEA. Moreover, the immunomodulatory role of DHEA will also be evaluated in different in vitro assays, in special, cell proliferation and function of Treg cells. Finally, the better understanding of the immunomodulatory capacity of the DHEA in experimentally induced intestinal inflammation may provide a scientific basis for the development of more effective therapeutic strategies for ulcerative colitis and/or Crohn's disease.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREITAS ALVES, VANESSA BEATRIZ; BASSO, PAULO JOSE; NARDINI, VIVIANI; SILVA, ANGELICA; LAZO CHICA, JAVIER EMILIO; DE BARROS CARDOSO, CRISTINA RIBEIRO. Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses. Immunobiology, v. 221, n. 9, p. 934-943, SEP 2016. (10/20162-7, 12/17265-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALVES, Vanessa Beatriz Freitas. Study of the immunomodulatory potential of Dehydroepiandrosterone (DHEA) in experimental intestinal inflammation. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.