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Participation of hypothalamus-pituitary-adrenal axis in experimental induced inflammatory bowel disease

Grant number: 12/00984-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2012
Effective date (End): April 15, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Cristina Ribeiro de Barros Cardoso
Grantee:Patrícia Reis de Souza
Home 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

Inflammmatory bowel diseases (IBD) like Crohn's disease are characterized by Th1 and Th17 exacerbated inflammatory response besides a lack of regulation by regulatory T cells (Tregs). Chronic stress is a risk factor for IBD development while the endocrine system may also play a regulatory role by producing glucocorticoids (GC) which are anti-inflammatory mediators that may induce Treg differentiation. On the other hand, some IBD patients are not responsive to corticosteroid therapy and only little information is available regarding this unresponsiveness or the GC effects on the IL-17/Treg balance on the inflamed mucosa. Then, our aim is to evaluate the involvement of the HPA axis and exogenous GC in the modulation of immune response in IBD, in special in the Th17/Treg balance. Experimental IBD will be induced in C57BL/6 mice which will have the adrenals removed or will be treated with GC. Weight, diarrhea, intestinal bleeding and the inflammatory response (neutrophils, eosinophils, Treg, Th17 cells) will be evaluated in gut segments, spleen and mesenteric lymph nodes. The quantification of GC will be performed in plasma and gut samples, while endocrine system modulation of IBD will be assessed by Th1, Th2, Th17 and Treg cytokine profile quantification in the colon of inflamed, controls, adrenalectomized or GC treated mice. Moreover, the suppressive capacity of Tregs from experimental animals will be evaluated by co-culture assays with effector CD4+CD25- cells and adequate stimuli. Finally, the understanding of the role of HPA axis and exogenous GC in the Th17/Treg balance may favor scientific basis for novel therapies aimed at IBD control.

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)
DE SOUZA, PATRICIA REIS; GUIMARAES, FRANCIELLE RODRIGUES; SALES-CAMPOS, HELIOSWILTON; BONFA, GIULIANO; NARDINI, VIVIANI; LAZO CHICA, JAVIER EMILIO; TURATO, WALTER MIGUEL; SILVA, JOAO SANTANA; ZAMBONI, DARIO SIMOES; DE BARROS CARDOSO, CRISTINA RIBEIRO. Absence of NOD2 receptor predisposes to intestinal inflammation by a deregulation in the immune response in hosts that are unable to control gut dysbiosis. Immunobiology, v. 223, n. 10, p. 577-585, OCT 2018. Web of Science Citations: 1.
SALES-CAMPOS, HELIOSWILTON; DE SOUZA, PATRICIA R.; BASSO, PAULO J.; NARDINI, VIVIANI; SILVA, ANGELICA; BANQUIERI, FERNANDA; ALVES, VANESSA B. F.; CHICA, JAVIER E. L.; NOMIZO, AURO; CARDOSO, CRISTINA R. B. Amelioration of experimental colitis after short-term therapy with glucocorticoid and its relationship to the induction of different regulatory markers. Immunology, v. 150, n. 1, p. 115-126, JAN 2017. Web of Science Citations: 6.
DE SOUZA, PATRICIA REIS; SALES-CAMPOS, HELIOSWILTON; BASSO, PAULO JOSE; NARDINI, VIVIANI; SILVA, ANGELICA; BANQUIERI, FERNANDA; FREITAS ALVES, VANESSA BEATRIZ; LAZO CHICA, JAVIER EMILIO; NOMIZO, AURO; DE BARROS CARDOSO, CRISTINA RIBEIRO. Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis. Mediators of Inflammation, 2016. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOUZA, Patrícia Reis de. Participation of the hypothalamic-pituitary-adrenal axis in experimentally induced inflammatory bowel disease. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.