Identification of endogenous pathways for the control of inflammation

• Grant number: 14/07328-4
• Support Opportunities: Research Projects - Thematic Grants
• Duration: December 01, 2014 - November 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Sandra Helena Poliselli Farsky
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Campa ; Cristiane Damas Gil ; Edgar Julian Paredes-Gamero ; Estela Maris Andrade Forell Bevilacqua ; Isabel Daufenback Machado ; Ivan da Rocha Pitta ; João Palermo Neto ; José Roberto Santin ; Ricardo Ambrósio Fock ; Sonia Maria Oliani
• Associated grant(s): 15/07812-6 - Multi-User Equipment approved in grant 2014/07328-4. Coordinator: Profa Sandra Helena Poliselli Farsky. Equipment: flow cytometer Accuri, AP.EMU
• Associated scholarship(s): 17/05430-4 - Effects of the interaction between annexin A1 and PPAR gamma upon development of experimental colitis, BP.DR; 16/19682-2 - Annexin A1 pathways triggered in the inflammatory bowel disease treated with infliximab, BP.DR; 16/20391-2 - Investigation of ANXA1 role on blastocyst implantation and uterine receptivity: ex vivo assays, BP.IC; 16/02903-6 - Role of annexin A1 in modulating granulopoiesis, BP.PD

Abstract

Inflammation is a primordial, complex and highly evolutionary-conserved active response mounted by the innate immune system in response to injury, xenobiotics exposure and infections in order to promote recovery. In addition, inflamamtion is relevant to some special conditions of the body, such as to the succesfull of gestation, and on obesity. Control of the inflammatory response is of Paramount importance in several physiological conditions to avoid pathologies. Indeed, the final goal of inflammation is not only to clear the microenvironment from harmful agents but also to restore tissue homeostasis and to stimulate healing processes where necessary. In its absence, injuries and infections wouldn't be rapidly countered, with unrelenting deterioration of the affected tissue and consequent risks for the entire organism. Therefore, inflammation is the basis of a diversity of diseases. Although widely studied, there is still need to decipher inflammation early stages with its mechanism and its resolution, particularly with the innovative therapeutic angle to identify drug which alt the inflammatory progress while helping resolution and healing.We among other (our collaborator Drs Egle Solito and Mauro Perretti- William Harvey Research Institute, School Medical and Dentistry, Queen Mary University of London (WHRI-SMD-QMUL, UK) have shown a clear role for Annexin A1 (ANXA1; an endogenous mediator of glucocorticoid action) in many biological systems (named granulopoiesis and reproduction) further supporting the idea of AnxA1 as therapeutic tool.Moreover in the lab we have also investigated the modulation of inflammation by peroxisome proliferator activated receptors (PPARs), as well as by the benzodiazepine peripheral receptor (TSPO). Activation of either target affords major modulation on the biology of the neutrophil, intriguingly, their expression, and/or function is controlled by endogenous glucocorticoids and by application of ANXA1. Based on our preliminary data this project aims to:1) Investigate the mechanisms of action of AnxA1 in controlling PMN, macrophage and microglia anti-inflammatory phenotype, focusing on granulopoesis; and the interplay with PPARs and TSPO functions in the peripheral and central nervous system ; 2) Investigate the molecular mechanisms of AnxA1 control on inflammation in reproduction;3) Investigate the role of TSPO in controlling cell differentiation and proliferation particularly in adipocytes responsible for regulating whole-body physiology. Collectivelly, the above aims will identify new targets and will guide on the viable approach for the generation of new molecules exploitable for innovative anti-inflammatory drugs, as well as drug formulations. Therefore, this proposal goes under the umbrella of a thematic project, it requires different expertise, with the involvement of multidisciplinary groups both national and international, to achieve its deliverables and, essentially, its success.This project will be based at the Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, USP (FCF-USP), which, among their research proposals, includes the investigation of the pathophysiology of inflammatory/imune, hematological and metabolic diseases, as well as neoplasia, in order to provide the basis for diagnostics and therapeutics strategies. This is the theme of the graduate program of the department - Pharmacy- Clinical Analyses - rated as 7 grades by CAPES in the Pharmacy area. Therefore, this Project is in accordance to goals of education and research of the Department of Clinical and Toxicological Analysis (FCF). (AU)

Scientific publications

(23)

(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)

SANDRI, SILVANA; HEBEDA, CRISTINA BICHELS; LOIOLA, RODRIGO AZEVEDO; CALGAROTO, SELMA; UCHIYAMA, MAYARA KLIMUK; ARAKI, KOITI; FRANK, LUIZA ABRAHAO; PAESE, KARINA; GUTERRES, SILVIA STANISCUASKI; POHLMANN, ADRIANA RAFFIN; et al. Direct effects of poly(epsilon-caprolactone) lipid-core nanocapsules on human immune cells. Nanomedicine, v. 14, n. 11, p. 1429-1442, JUN 2019. (14/07328-4)

PANTALEAO, LORENA; OLIVEIRA ROCHA, GUSTAVO HENRIQUE; REUTELINGSPERGER, CHRIS; TIAGO, MANOELA; MARIA-ENGLER, SILVYA STUCCHI; SOLITO, EGLE; FARSKY, SANDRA P.. Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells. Experimental Cell Research, v. 367, n. 2, p. 282-290, JUN 15 2018. (14/07328-4, 13/25903-3)

SCHARF, PABLO; DA ROCHA, GUSTAVO H. O.; SANDRI, SILVANA; HELUANY, CINTIA S.; PEDREIRA FILHO, WALTER R.; FARSKY, SANDRA H. P.. Immunotoxic mechanisms of cigarette smoke and heat-not-burn tobacco vapor on Jurkat T cell functions. Environmental Pollution, v. 268, n. B, JAN 1 2021. (19/19573-7, 14/07328-4)

OLIVEIRA DA ROCHA, GUSTAVO HENRIQUE; LOIOLA, RODRIGO AZEVEDO; PANTALEAO, LORENA DO NASCIMENTO; REUTELINGSPERGER, CHRIS; SOLITO, EGLE; POLISELLI FARSKY, SANDRA HELENA. Control of expression and activity of peroxisome proliferated-activated receptor gamma by Annexin A1 on microglia during efferocytosis. Cell Biochemistry and Function, v. 37, n. 7, p. 560-568, OCT 2019. (14/07328-4)

DE PAULA-SILVA, MARINA; ELISABETH BARRIOS, BIBIANA; MACCIO-MARETTO, LISA; SENA, ANGELA APARECIDA; FARSKY, SANDRA HELENA POLISELLI; GRACIELA CORREA, SILVIA; OLIANI, SONIA MARIA. Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis. Biochemical Pharmacology, v. 115, p. 104-113, SEP 1 2016. (14/07328-4)

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. (16/02012-4, 14/07328-4)

DREWES, CARINE C.; ALVES, ALINE DE C. S.; HEBEDA, CRISTINA B.; COPETTI, ISABELA; SANDRI, SILVANA; UCHIYAMA, MAYARA K.; ARAKI, KOITI; GUTERRES, SILVIA S.; POHLMANN, ADRIANA R.; FARSKY, SANDRA H.. Role of poly(epsilon-caprolactone) lipid-core nanocapsules on melanoma-neutrophil crosstalk. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 12, p. 7153-7163, 2017. (14/07328-4, 10/19802-1)

KANDA KUPA, LEONARD DE VINCI; DREWES, CARINE C.; BARIONI, ERIC D.; NEVES, CAMILA L.; SAMPAIO, SANDRA COCCUZZO; FARSKY, SANDRA H. P.. Role of Translocator 18 KDa Ligands in the Activation of Leukotriene B4 Activated G-Protein Coupled Receptor and Toll Like Receptor-4 Pathways in Neutrophils. FRONTIERS IN PHARMACOLOGY, v. 8, OCT 27 2017. (14/07328-4)

HELUANY, CINTIA SCUCUGLIA; KANDA KUPA, LEONARD DE VINCI; VIANAB, MARIANA NASCIMENTO; FERNANDES, CRISTINA MARIA; POLISELLI FARSKY, SANDRA HELENA. Hydroquinone exposure worsens the symptomatology of rheumatoid arthritis. Chemico-Biological Interactions, v. 291, p. 120-127, AUG 1 2018. (14/07328-4)

CLARET PEREIRA, NATALIA RUBIO; LOIOLA, RODRIGO AZEVEDO; RODRIGUES, STEPHEN FERNANDES; DE OLIVEIRA, CATIUSCIA P.; BUTTENBENDER, SABRINA L.; GUTERRES, SILVIA S.; POHLMANN, ADRIANA R.; FARSKY, SANDRA H.. Mechanisms of the effectiveness of poly(epsilon-caprolactone) lipid-core nanocapsules loaded with methotrexate on glioblastoma multiforme treatment. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 13, p. 4563-4573, 2018. (11/02438-8, 14/07328-4)

MACHADO, ISABEL DAUFENBACK; SPATTI, MARINA; HASTREITER, ARACELI; SANTIN, JOSE ROBERTO; FOCK, RICARDO AMBROSIO; GIL, CRISTIANE DAMAS; OLIANI, SONIA MARIA; PERRETTI, MAURO; POLISELLI FARSKY, SANDRA HELENA. Annexin A1 Is a Physiological Modulator of Neutrophil Maturation and Recirculation Acting on the CXCR4/CXCL12 Pathway. Journal of Cellular Physiology, v. 231, n. 11, p. 2418-2427, NOV 2016. (10/16828-0, 14/07328-4)

ALI, BAKAT; KUPA, LEONARD D. KANDA; HELUANY, CINTIA S.; DREWES, CARINE C.; VASCONCELOS, STANLEY N. S.; FARSKY, SANDRA H. P.; STEFANI, HELIO A.. Cytotoxic effects of a novel maleimide derivative on epithelial and tumor cells. BIOORGANIC CHEMISTRY, v. 72, p. 199-207, JUN 2017. (13/17960-7, 12/17954-4, 12/00424-2, 10/19802-1, 14/07328-4)

SCHARF, PABLO; BROERING, MILENA FRONZA; OLIVEIRA DA ROCHA, GUSTAVO HENRIQUE; FARSKY, SANDRA HELENA POLISELLI. Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 19, OCT 2020. (17/05430-4, 19/19573-7, 18/26383-7, 14/07328-4)

UCHIYAMA, MAYARA K.; HEBEDA, CRISTINA B.; SANDRI, SILVANA; PAULA-SILVA, MARINA DE; ROMANO, MARIANA; CARDOSO, ROBERTA M.; TOMA, SERGIO H.; ARAKI, KOITI; FARSKY, SANDRA H. P.. In vivo evaluation of toxicity and anti-inflammatory activity of iron oxide nanoparticles conjugated with ibuprofen. Nanomedicine, v. 16, n. 9, APR 2021. (18/21489-1, 14/07328-4)

HELUANY, CINTIA SCUCUGLIA; DONATE, PAULA BARBIM; SCHNEIDER, AYDA HENRIQUES; FABRIS, ANDRE LUIS; GOMES, RENAN AUGUSTO; VILLAS-BOAS, ISADORA MARIA; TAMBOURGI, DENISE VILARINHO; DA SILVA, TARCILIA APARECIDA; TROSSINI, GUSTAVO HENRIQUE GOULART; NALESSO, GIOVANNA; et al. Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways. ANTIOXIDANTS, v. 10, n. 6, JUN 2021. (19/19573-7, 14/07328-4)

DA ROCHA, GUSTAVO HENRIQUE OLIVEIRA; DE PAULA-SILVA, MARINA; BROERING, MILENA FRONZA; SCHARF, PABLO RHASAN DOS SANTOS; MATSUYAMA, LARISSA SATIKO ALCANTARA SEKIMOTO; MARIA-ENGLER, SILVYA STUCHI; FARSKY, SANDRA HELENA POLISELLI. Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages. FRONTIERS IN PHARMACOLOGY, v. 11, DEC 21 2020. (16/19682-2, 17/05430-4, 14/07328-4)

FABRIS, ANDRE LUIS; NUNES, ANDRE VINICIUS; SCHUCH, VIVIANE; DE PAULA-SILVA, MARINA; ROCHA, G. H. O.; NAKAYA, HELDER I.; HO, PAULO LEE; SILVEIRA, EDUARDO L. V.; POLISELLI FARSKY, SANDRA HELENA. Hydroquinone exposure alters the morphology of lymphoid organs in vaccinated C57Bl/6 mice. Environmental Pollution, v. 257, FEB 2020. (16/24134-4, 14/07328-4)

DE PAULA-SILVA, MARINA; OLIVEIRA DA ROCHA, GUSTAVO HENRIQUE; BROERING, MILENA FRONZA; QUEIROZ, MARIA LUIZA; SANDRI, SILVANA; LOIOLA, RODRIGO AZEVEDO; OLIANI, SONIA MARIA; VIEIRA, ANDREA; PERRETTI, MAURO; POLISELLI FARSKY, SANDRA HELENA. Formyl Peptide Receptors and Annexin A1: Complementary Mechanisms to Infliximab in Murine Experimental Colitis and Crohn's Disease. FRONTIERS IN IMMUNOLOGY, v. 12, SEP 17 2021. (14/07328-4, 19/02806-9, 16/19682-2)

DE PAULA-SILVA, MARINA; BROERING, MILENA FRONZA; SCHARF, PABLO; OLIVEIRA DA ROCHA, GUSTAVO HENRIQUE; FARSKY, SANDRA; LINO-DOS-SANTOS-FRANCO, ADRIANA. Red light-emitting diode treatment improves tissue recovery in DSS-induced colitis in mice. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 212, NOV 2020. (14/07328-4)

HEBEDA, CRISTINA B.; SANDRI, SILVANA; BENIS, CLAUDIA M.; DE PAULA-SILVA, MARINA; LOIOLA, RODRIGO A.; REUTELINGSPERGER, CHRIS; PERRETTI, MAURO; FARSKY, SANDRA H. P.. Annexin A1/Formyl Peptide Receptor Pathway Controls Uterine Receptivity to the Blastocyst. CELLS, v. 9, n. 5, MAY 2020. (14/07328-4)

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. (13/07487-2, 12/13041-4, 12/21603-2, 16/02012-4, 10/19802-1, 14/07328-4)

HELUANY, CINTIA SCUCUGLIA; KANDA KUPA, LEONARD DE VINCI; VIANA, MARIANA NASCIMENTO; FERNANDES, CRISTINA MARIA; VOLPE SILVEIRA, EDUARDO LANI; POLISELLI FARSKY, SANDRA HELENA. In vivo exposure to hydroquinone during the early phase of collagen-induced arthritis aggravates the disease. Toxicology, v. 408, p. 22-30, SEP 1 2018. (14/07328-4)

BARBOSA, V, CHRISTIANO M.; FOCK, RICARDO AMBROSIO; HASTREITER, ARACELI APARECIDA; REUTELINGSPERGER, CRIS; PERRETTI, MAURO; PAREDES-GAMERO, EDGAR J.; FARSKY, SANDRA H. P.. Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway. CELL DEATH DISCOVERY, v. 5, SEP 23 2019. (16/02903-6, 14/07328-4)