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Lipid mediators as regulators of immune response

Grant number: 09/07169-5
Support Opportunities:Research Projects - Thematic Grants
Duration: December 01, 2009 - July 31, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Lúcia Helena Faccioli
Grantee:Lúcia Helena Faccioli
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers:Alexandra Ivo de Medeiros ; Auro Nomizo ; Carlos Arterio Sorgi ; Celio Lopes Silva ; Claudia da Silva Bitencourt ; Edson Garcia Soares ; Elaine Cristina Pereira de Martinis ; Fabiani Gai Frantz ; Roberto Nicolete ; Simone Gusmão Ramos ; Vanderlei Rodrigues ; Vânia Luiza Deperon Bonato
Associated grant(s):13/11612-7 - 13th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, AR.EXT
Associated scholarship(s):11/23992-3 - Biological studies of the enzyme hyaluronidase and its possible influence in the skin wound healing process, BP.PD
11/01845-9 - Study of intracellular signaling involved in eicosanoid production which are dependent on the expression of phospholipase C from Mycobacterium tuberculosis, BP.DR
11/04704-7 - Role of erythropoietin Histoplasma capsulatum infection, BP.MS
10/18179-9 - Tityus serrulatus scorpion venom is recognized by pattern recognition receptors and induces cell activation and inflammation, BP.DD
10/13204-5 - Lipid Bodies Formation and Eicosanoids Generation In Vitro Infections by Different Strains of Mycobacterium tuberculosis Isolated from Humans, BP.IC


Leukotrienes (LTs) and prostaglandines (PGs) regulate the immune response in infections and other pathologies. In last years, we have contributed for the understanding of the role of LTs and PGs in infections and vaccinal processes. We have shown that LTs are essential for defense mechanisms in histoplasmosis, tuberculosis, and strongyloidiasis, acting as adjuvants and recruiting effector cells. However, these mediators favor infections in trypanosomiasis and candidiasis. Referring to PGs, we have shown that these contribute for pathogenesis of histoplasmosis and strongyloidiasis. Knowing that LTs and PGs are unstable, we have developed a methodology of encapsulation in biocompatible polymers, and we have shown that this process preserves their biological activities, thus representing a new strategy for therapeutic intervention. In this project, formed by 09 subprojects, we will proceed the studies on LTs and PGs in the regulation of innate or induced immune response and the use of these mediators in therapies. In this context, our objectives are (a) to investigate the role of LTs and PGs in the effector mechanisms of macrophages infected by Cronobacter sakazakii; (b) to determine the relationship among lipidic mediators and (b1) infectivity/pathogenicity of strains of Mycobacterium tuberculosis isolated from patients with different clinical forms of the disease, (b2) susceptibility and resistance in the infection by Histoplasma capsulatum, (b3) different methods of vaccination ("prime-booster", gene transfection by electroporation or bioballistics); (c) to develop formulations containing lipidic mediators or their inhibitors associated or not to antigens as vaccinal or therapeutic strategies. Our studies shall widen the understanding on effector mechanisms of immune response that are regulated by LTs and PGs, contribute for development of new therapeutic strategies, form human resources in multidisciplinary areas, and set new methodologies in the College of Pharmaceutical Science of Ribeirão Preto. (AU)

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Scientific publications (15)
(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)
ZOCCAL, KARINA FURLANI; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; BITENCOURT, CLAUDIA DA SILVA; SORGI, CARLOS ARTERIO; FIGUEIREDO BORDON, KARLA DE CASTRO; ARANTES, ELIANE CANDIANI; FACCIOLI, LUCIA HELENA. PPAR-gamma activation by Tityus serrulatus venom regulates lipid body formation and lipid mediator production. Toxicon, v. 93, p. 90-97, . (09/07169-5)
FRONZA, MARCIO; CAETANO, GUILHERME F.; LEITE, MARCEL N.; BITENCOURT, CLAUDIA S.; PAULA-SILVA, FRANCISCO W. G.; ANDRADE, THIAGO A. M.; FRADE, MARCO A. C.; MERFORT, IRMGARD; FACCIOLI, LUCIA H.. Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing. PLoS One, v. 9, n. 11, . (11/23992-3, 09/07169-5)
ZOCCAL, KARINA FURLANI; BITENCOURT, CLAUDIA DA SILVA; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; SORGI, CARLOS ARTERIO; FIGUEIREDO BORDON, KARLA DE CASTRO; ARANTES, ELIANE CANDIANI; FACCIOLI, LUCIA HELENA. TLR2, TLR4 and CD14 Recognize Venom-Associated Molecular Patterns from Tityus serrulatus to Induce Macrophage-Derived Inflammatory Mediators. PLoS One, v. 9, n. 2, . (10/18179-9, 09/07169-5)
TARTARI PEREIRA, PRISCILLA APARECIDA; BITENCOURT, CLAUDIA DA SILVA; DOS SANTOS, DAIANE FERNANDA; NICOLETE, ROBERTO; GELFUSO, GUILHERME MARTINS; FACCIOLI, LUCIA HELENA. Prostaglandin D-2-loaded microspheres effectively activate macrophage effector functions. European Journal of Pharmaceutical Sciences, v. 78, p. 132-139, . (09/05106-6, 09/07169-5)
SORGI, CARLOS ARTERIO; SOARES, ELYARA MARIA; ROSADA, ROGERIO SILVA; BITENCOURT, CLAUDIA SILVA; ZOCCAL, KARINA FURLANI; TARTARI PEREIRA, PRISCILLA APARECIDA; FONTANARI, CAROLINE; BRANDAO, IZAIRA; MASSON, ANA PAULA; RAMOS, SIMONE GUSMAO; et al. Eicosanoid pathway on host resistance and inflammation during Mycobacterium tuberculosis infection is comprised by LTB4 reduction but not PGE(2) increment. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1866, n. 3, . (10/11239-6, 15/00658-1, 09/07169-5)
PEREIRA, PRISCILLA A. T.; ASSIS, PATRICIA A.; PRADO, MORGANA K. B.; RAMOS, SIMONE G.; ARONOFF, DAVID M.; DE PAULA-SILVA, FRANCISCO W. G.; SORGI, CARLOS A.; FACCIOLI, LUCIA H.. Prostaglandins D-2 and E-2 have opposite effects on alveolar macrophages infected with Histoplasma capsulatum. Journal of Lipid Research, v. 59, n. 2, p. 195-206, . (09/07169-5, 14/07125-6)
BITENCOURT, CLAUDIA DA SILVA; DA SILVA, LETICIA BUENO; TARTARI PEREIRA, PRISCILLA APARECIDA; GELFUSO, GUILHERME MARTINS; FACCIOLI, LUCIA HELENA. Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 136, p. 678-686, . (07/04741-4, 02/12856-2, 09/07169-5, 05/54855-0)
ZOCCAL, KARINA FURLANI; BITENCOURT, CLAUDIA DA SILVA; SECATTO, ADRIANA; SORGI, CARLOS ARTERIO; FIGUEREDO BORDON, KARLA DE CASTRO; SAMPAIO, SUELY VILELA; ARANTES, ELIANE CANDIANI; FACCIOLI, LUCIA HELENA. Tityus serrulatus venom and toxins Ts1, Ts2 and Ts6 induce macrophage activation and production of immune mediators. Toxicon, v. 57, n. 7-8, p. 1101-1108, . (05/54855-0, 09/07169-5, 09/09829-2)
ASSIS, PATRICIA A.; ESPINDOLA, MILENA S.; PAULA-SILVA, FRANCISCO W. G.; RIOS, WENDY M.; PEREIRA, PRISCILLA A. T.; LEAO, SYLVIA C.; SILVA, CELIO L.; FACCIOLI, LUCIA H.. Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages. BMC Microbiology, v. 14, . (09/07169-5, 11/01845-9)
ESPINDOLA, MILENA SOBRAL; FRANTZ, FABIANI GAI; SOARES, LUANA SILVA; MASSON, ANA PAULA; TEFE-SILVA, CRISTIANE; BITENCOURT, CLAUDIA SILVA; OLIVEIRA, SERGIO COSTA; RODRIGUES, VANDERLEI; RAMOS, SIMONE GUSMAO; SILVA, CELIO LOPES; et al. Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+memory T cells, reduces chronic pathology and decreases egg viability during Schistosoma mansoni infection. BMC INFECTIOUS DISEASES, v. 14, . (09/01501-8, 09/07169-5)
ROGERIO, ALEXANDRE P.; SA-NUNES, ANDERSON; FACCIOLI, LUCIA H.. The activity of medicinal plants and secondary metabolites on eosinophilic inflammation. PHARMACOLOGICAL RESEARCH, v. 62, n. 4, p. 298-307, . (09/07169-5)
LOCACHEVIC, GISELE APARECIDA; TARTARI PEREIRA, PRISCILLA APARECIDA; SECATTO, ADRIANA; FONTANARI, CAROLINE; GALVAO, ALYNE FAVERO; BORGES PRADO, MORGANA KELLY; ZOCCAL, KARINA FURLANI; PETTA, TANIA; BERALDO MORAES, LUIZ ALBERTO; RAMOS, SIMONE GUSMAO; et al. Erythropoietin Exacerbates Inflammation and Increases the Mortality of Histoplasma capsulatum-Infected Mice. Mediators of Inflammation, . (09/07169-5, 11/04704-7)
PEREIRA, PRISCILLA A. T.; BITENCOURT, CLAUDIA S.; REIS, MOUZARLLEM B.; FRANTZ, FABIANI G.; SORGI, CARLOS A.; SOUZA, CAMILA O. S.; SILVA, CELIO L.; GARDINASSI, LUIZ G.; FACCIOLI, LUCIA H.. Immunomodulatory activity of hyaluronidase is associated with metabolic adaptations during acute inflammation. Inflammation Research, v. 69, n. 1, . (07/04741-4, 14/07125-6, 09/07169-5, 15/00658-1)
PUCCA, MANUELA B.; PEIGNEUR, STEVE; COLOGNA, CAMILA T.; CERNI, FELIPE A.; ZOCCAL, KARINA F.; BORDON, KARLA DE C. F.; FACCIOLI, LUCIA H.; TYTGAT, JAN; ARANTES, ELIANE C.. Electrophysiological characterization of the first Tityus serrulatus alpha-like toxin, Ts5: Evidence of a pro-inflammatory toxin on macrophages. Biochimie, v. 115, p. 8-16, . (13/21342-7, 14/03332-7, 13/21329-0, 09/07169-5, 13/26200-6)

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