The role of hypothalamus-pituitary-adrenal (HPA) axis and exogenous glucocorticoids in the modulation of immune response in inflammatory bowel disease

• Grant number: 10/20162-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: November 01, 2011
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Cristina Ribeiro de Barros Cardoso
• Grantee: Cristina Ribeiro de Barros Cardoso
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: João Santana da Silva ; Lúcia Helena Faccioli
• Associated scholarship(s): 13/11042-6 - Evaluation of the immune modulatory effects of statins and glucocorticoids in experimental colitis, BP.MS; 12/17265-4 - Study of the immunomodulatory potential of Dehydroepiandrosterone (DHEA) in experimental intestinal inflammation, BP.DR; 12/00984-8 - Participation of hypothalamus-pituitary-adrenal axis in experimental induced Inflammatory Bowel Disease, BP.DR

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 along with T-Bet, GATA-3, Foxp3 and RORgammat expression 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. (AU)

Scientific publications

(14)

(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)

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. (10/20162-7, 12/00984-8)

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)

P.J. BASSO; M.T.C. FONSECA; G. BONFÁ; V.B.F. ALVES; H. SALES-CAMPOS; V. NARDINI; C.R.B. CARDOSO. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease. Brazilian Journal of Medical and Biological Research, v. 47, n. 9, p. 727-737, 2014-07-25. (10/20162-7)

DUARTE-SILVA, MURILLO; AFONSO, POLIANA CRISTINA; DE SOUZA, PATRICIA REIS; PEGHINI, BETHANEA CREMA; RODRIGUES-JUNIOR, VIRMONDES; DE BARROS CARDOSO, CRISTINA RIBEIRO. Reappraisal of antibodies against Saccharomyces cerevisiae (ASCA) as persistent biomarkers in quiescent Crohn's disease. AUTOIMMUNITY, v. 52, n. 1, p. 37-47, JAN 2 2019. (10/20162-7)

BASSO, PAULO JOSE; SALES-CAMPOS, HELIOSWILTON; NARDINI, VIVIANI; DUARTE-SILVA, MURILLO; FREITAS ALVES, VANESSA BEATRIZ; BONFA, GIULIANO; RODRIGUES, CASSIANO COSTA; GHIROTTO, BRUNO; LAZO CHICA, JAVIER EMILIO; NOMIZO, AURO; et al. Peroxisome Proliferator-Activated Receptor Alpha Mediates the Beneficial Effects of Atorvastatin in Experimental Colitis. FRONTIERS IN IMMUNOLOGY, v. 12, AUG 9 2021. (10/20162-7, 17/08651-1, 13/11042-6)

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, v. 2016, p. 13-pg., 2016-01-01. (12/00984-8, 10/20162-7)

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. 12-pg., 2017-01-01. (12/00984-8, 10/20162-7)

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. (10/20162-7, 12/00984-8)

TURATO, WALTER MIGUEL; SALES-CAMPOS, HELIOSWILTON; MORENO BRAGA, CAMILA BITU; CARVALHO CUNHA, SELMA FREIRE; SILVAH, JOSE HENRIQUE; DA SILVA, JOAO SANTANA; MARCHINI, JULIO SERGIO; DE BARROS CARDOSO, CRISTINA RIBEIRO. The impact of intestinal resection on the immune function of short bowel syndrome patients. HUMAN IMMUNOLOGY, v. 77, n. 12, p. 1202-1208, DEC 2016. (10/20162-7)

SALES-CAMPOS, HELIOSWILTON; DE SOUZA, PATRICIA REIS; BASSO, PAULO JOSE; RAMOS, ANDERSON DANIEL; NARDINI, VIVIANI; LAZO CHICA, JAVIER EMILIO; CAPURRO, MARGARETH LARA; SA-NUNES, ANDERSON; DE BARROS CARDOSO, CRISTINA RIBEIRO. Aedes aegypti salivary gland extract ameliorates experimental inflammatory bowel disease. International Immunopharmacology, v. 26, n. 1, p. 13-22, MAY 2015. (09/09892-6, 10/20162-7)

SALES-CAMPOS, H.; BASSO, P. J.; ALVES, V. B. F.; FONSECA, M. T. C.; BONFA, G.; NARDINI, V.; CARDOSO, C. R. B.. Classical and recent advances in the treatment of inflammatory bowel diseases. Brazilian Journal of Medical and Biological Research, v. 48, n. 2, p. 96-107, FEB 2015. (10/20162-7)

GUIMARAES, FRANCIELLE RODRIGUES; SALES-CAMPOS, HELIOSWILTON; NARDINI, VIVIANI; DA COSTA, THIAGO ALVARES; COSTA FONSECA, MONIQUE THAIS; RODRIGUES JUNIOR, VIRMONDES; SORGI, CARLOS ARTERIO; DA SILVA, JOAO SANTANA; LAZO CHICA, JAVIER EMILIO; FACCIOLI, LUCIA HELENA; et al. The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and improves cutaneous wound healing. Clinical Immunology, v. 190, p. 74-83, MAY 2018. (10/20162-7)

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. (10/20162-7, 12/00984-8)

FREITAS ALVES, V. B.; COUTINHO DE SOUSA, B.; THAIS COSTA FONSECA, M.; OGATA, H.; CALIARI-OLIVEIRA, C.; NAVARRO UEDA YAOCHITE, J.; RODRIGUES JUNIOR, V.; LAZO CHICA, J. E.; SANTANA DA SILVA, J.; RIBEIRO MALMEGRIM, K. C.; et al. A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v. 196, n. 2, p. 139-154, MAY 2019. (10/20162-7)

Filed patent(s) as a result of this research project