Mediators involved in the genesis of pain and the migration of leukocytes and in sepsis

• Grant number: 07/51247-5
• Support Opportunities: Research Projects - Thematic Grants
• Duration: November 01, 2007 - April 30, 2012
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Sérgio Henrique Ferreira
• Grantee: Sérgio Henrique Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais:( Últimos ): Fernando de Queiroz Cunha ; Thiago Mattar Cunha
• Pesquisadores principais:( Antigos ): John Stephen Hothersall ; Lewis Joel Greene
• Associated scholarship(s): 11/03293-3 - Role of Nox2 derived products in the pathogenesis of sepsis, BP.DR; 08/10582-9 - Central and peripheral mechanisms involved in the antinociception produced by cannabinoids agonists, BP.PD; 09/10853-5 - Effects of the glycosilation of the proteins alpha-1-acid glycoprotein and hemopexin on the inhibition of neutrophil migration in experimental sepsis, BP.PD; + associated scholarships 09/07651-1 - Role of liver X Receptor-LXRs in the modulation of local and systemic response during sepsis, BP.DR; 08/11593-4 - PARTICIPATION OF NOD-LIKE RECEPTORS ON INFLAMMATORY RESPONSE IN POLYMICROBIAL SEPSIS, BP.DR; 08/01434-6 - Role of IL-10 and IFN-gamma in orthodontic tooth movement in mice, BP.DR; 08/04391-6 - Role of PI3Kg/AKT/nitric oxide/K+(ATP) channels signaling pathway on peripheral antinociceptive effect of dipyrone, BP.PD; 07/07428-5 - Participation of satellites cells in mechanical inflammatory hypernociception, and characterization of prostanoid receptors in these cells, BP.DR - associated scholarships

Abstract

Our project consists of 3 subprojects which investigate a) mechanisms involved in the genesis of chronic and acute inflammatory pain as well as the mechanisms involved in the effects of different analgesics; b) mediators involved in the migration of neutrophils in different models of immune inflammation; c) mechanisms involved in the failure of the migration of neutrophils to the site of infection observed in serious sepsis. [...]. At molecular level we aim to determine the signaling paths and the transcription factors involved in sensibilization. Equally we will investigate molecular mechanisms involved in the analgesic actions of morphine and cannabinoids. As for mechanisms involved in the migration of leukocytes we intend to determine which cytokines, chemocines and their receptors are involved in the recruitment of leukocytes in different models of inflammatory diseases as well as the mechanisms by which these mediators induce migration. The modulating role of NO, CO, H2S, and PGJ2 on the migration will also be determined. It is intended also to determine the mechanisms by which salivas of vector insects modulate the inflammatory response. Finally, using in vivo and in vitro models we will determine the mechanisms involved in the failure of the migration of neutrophils in sepsis, focusing on the role of cytokines/chemocines, free radicals, Toll-like receptors, rolling/adhesion of neutrophils on the vascular endothelium, signaling paths and transcription factors and also the role of desensibilization of receptors for chemotaxic agents. (AU)

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)

SOUTO, FABRICIO O.; ALVES-FILHO, JOSE C.; TURATO, WALTER M.; AUXILIADORA-MARTINS, MARIA; BASILE-FILHO, ANIBAL; CUNHA, FERNANDO Q.. Essential Role of CCR2 in Neutrophil Tissue Infiltration and Multiple Organ Dysfunction in Sepsis. American Journal of Respiratory and Critical Care Medicine, v. 183, n. 2, p. 234-242, JAN 15 2011. (07/51247-5)