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Evaluation of the immunomodulatory activity of Annexin A1 protein in the regulation of inflammatory disorders of the gastrointestinal system: studies in vivo and in vitro experimental models

Grant number: 16/02012-4
Support type:Regular Research Grants
Duration: July 01, 2016 - September 30, 2018
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Sonia Maria Oliani
Grantee:Sonia Maria Oliani
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
Assoc. researchers: Mauro Perretti ; Silvia Graciela Correa

Abstract

. The protein annexin A1 (AnxA1) acts on the resolution of inflammation and has beenassociated to gastrointestinal mucosa protection. Several surveys have shown the protective effect ofAnxA1 in acute inflammation, regulating the influx of neutrophils, monocytes and mast celldegranulation and, in chronic inflammatory processes acting in response to infections and neoplasias. Forthese reasons, our investigation seeks to evaluate the involvement of this protein in the break of intestinalimune tolerance, resulting in ulcerative colitis (UK), and in the microenvironmental response tocarcinogenic damage. Initially, in the chemically induced colitis model, the objective is to investigateAnxA1 expression and the cytokines production in wild mice (WT) treated with anti-TNF-a neutralizer,while the AnxA1 deficient (AnxA1-/-) ones will be used to test this protein in mediating TNF-a blockageduring acute intestinal inflammation. In colorectal cancer (CRC), the AnxA1 expression is unregulatedand affects the growth and malignant transformation of colonic tumors. Thus, mast cells, because of theirheterogeneity and importance in this setting, will be evaluated as to the production of post tumormediators in WT and AnxA1-/- mice exposed to chemical carcinogenesis. Finally, using an in vitromodel, human mast cell and colon tumor cell lines will be co-cultured in hypoxia with the addition of theAc2-26 peptide of the AnxA1 to evaluate the effect on the synthesis of protumoral mediators. In theproposed investigations, the clinical, histopatholocial and molecular parameters evaluated will allow for abetter understanding of the role of AnxA1 in regulating the inflamatory intestinal microenvironment, and,possibly, to result in an effective contribution to preventive and therapeutic applications. (AU)

Scientific publications (10)
(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)
CARDIN, LAILA TONIOL; PRATES, JANESLY; DA CUNHA, BIANCA RODRIGUES; TAJARA, ELOIZA HELENA; OLIANI, SONIA MARIA; RODRIGUES-LISONI, FLAVIA CRISTINA. Annexin A1 peptide and endothelial cell-conditioned medium modulate cervical tumorigenesis. FEBS OPEN BIO, v. 9, n. 4, p. 668-681, APR 2019. Web of Science Citations: 0.
GIMENES, ALEXANDRE D.; ANDRADE, BRUNA F. D.; PINOTTI, JOSE VICTOR P.; OLIANI, SONIA M.; GALVIS-ALONSO, ORFA Y.; GIL, CRISTIANE D. Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced status epilepticus model: anti-inflammatory and neuroprotective effects. JOURNAL OF NEUROINFLAMMATION, v. 16, FEB 12 2019. Web of Science Citations: 1.
MARMORATO, MARIANA PRADO; GIMENES, ALEXANDRE DANTAS; COSTA ANDRADE, FRANS EBERTH; OLIANI, SONIA MARIA; GIL, CRISTIANE DAMAS. Involvement of the annexin A1-Fpr anti-inflammatory system in the ocular allergy. European Journal of Pharmacology, v. 842, p. 298-305, JAN 5 2019. Web of Science Citations: 2.
DE OLIVEIRA CARDOSO, MARYSTELA FAVERO; MORELI, JUSCIELE BROGIN; GOMES, ANGELICA OLIVEIRA; ZANON, CAROLINE DE FREITAS; SILVA, ANA ELIZABETE; PAULESU, LUANA RICCI; IETTA, FRANCESCA; MINEO, JOSE ROBERTO; FERRO, ELOISA AMALIA; OLIANI, SONIA MARIA. Annexin A1 peptide is able to induce an anti-parasitic effect in human placental explants infected by Toxoplasma gondii. Microbial Pathogenesis, v. 123, p. 153-161, OCT 2018. Web of Science Citations: 1.
LACERDA, JESSICA ZANI; DREWES, CARINE CRISTIANE; OLIVEIRA MIMURA, KALLYNE KIOKO; ZANON, CAROLINE DE FREITAS; ANSARI, TAHERA; GIL, CRISTIANE DAMAS; GRECO, KARIN VICENTE; POLISELLI FARSKY, SANDRA HELENA; OLIANI, SONIA MARIA. Annexin A1(2-26) Treatment Improves Skin Heterologous Transplantation by Modulating Inflammation and Angiogenesis Processes. FRONTIERS IN PHARMACOLOGY, v. 9, SEP 10 2018. Web of Science Citations: 1.
HEBEDA, CRISTINA B.; MACHADO, ISABEL D.; REIF-SILVA, ISADORA; MORELI, JUSCIELE B.; OLIANI, SONIA M.; NADKARNI, SUCHITA; PERRETTI, MAURO; BEVILACQUA, ESTELA; FARSKY, SANDRA H. P. Endogenous annexin A1 (AnxA1) modulates early-phase gestation and offspring sex-ratio skewing. Journal of Cellular Physiology, v. 233, n. 9, p. 6591-6603, SEP 2018. Web of Science Citations: 1.
MELLO-BOSNIC, CLAUDIA; GIMENES, ALEXANDRE DANTAS; OLIANI, SONIA MARIA; GIL, CRISTIANE DAMAS. Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis. European Journal of Pharmacology, v. 833, p. 124-130, AUG 15 2018. Web of Science Citations: 1.
CARLOS, CARLA P.; SILVA, ANALICE A.; GIL, CRISTIANE D.; OLIANI, SONIA M. Pharmacological treatment with galectin-1 protects against renal ischaemia-reperfusion injury. SCIENTIFIC REPORTS, v. 8, JUN 22 2018. Web of Science Citations: 2.
MOLAS, RAFAELA BATISTA; DE PAULA-SILVA, MARINA; MASOOD, REHANA; ULLAH, ANWAR; GIMENES, ALEXANDRE DANTAS; OLIANI, SONIA MARIA. AC(2-26) peptide and serine protease of Bothrops atrox similarly induces angiogenesis without triggering local and systemic inflammation in a murine model of dorsal skinfold chamber. Toxicon, v. 137, p. 7-14, OCT 2017. Web of Science Citations: 2.
CARDIN, LAILA TONIOL; SONEHARA, NATHALIA MARTINS; OLIVEIRA MIMURA, KALLYNE KIOKO; DINARTE DOS SANTOS, ANEMARI RAMOS; DA SILVA JUNIOR, WILSON ARAUJO; SOBRAL, LAYS MARTIN; LEOPOLDINO, ANDREIA MACHADO; DA CUNHA, BIANCA RODRIGUES; TAJARA, ELOIZA H.; OLIANI, SONIA MARIA; RODRIGUES-LISONI, FLAVIA CRISTINA. ANXA1(Ac2-26) peptide, a possible therapeutic approach in inflammatory ocular diseases. Gene, v. 614, p. 26-36, MAY 30 2017. Web of Science Citations: 3.

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