"EFFECTS OF 2-AG, THROUGH MONOACYLGLYCEROL LIPASE INHIBITION, IN A MURINE MODEL OF ACUTE LUNG INJURY LPS-INDUCED"

• Grant number: 11/10181-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2011
• End date: August 31, 2014
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: João Palermo Neto
• Grantee: Carolina Costola de Souza Pavani
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/51886-3 - Neuroimmunomodulation: drugs, stress and cytokines on nervous, endocrine and immune systems relationships, AP.TEM

Abstract

The neuroimmunomodulation is defined as the area that studies the interrelationships between the Central Nervous System (CNS) and the Immune System (IS). The receptors and their ligands ubiquitous distribution are of vital importance for the establishment of two-way communication between these large systems. Thus, the endocannabinoid system (SE) seems to fit perfectly in the context of the molecular basis of the immune-neuro-endocrine interaction. This system is known to regulate a number of physiological functions such as movement, memory, learning, cognition, appetite, emesis, body temperature, pain behavior and neuroendocrine secretion. Furthermore, it has been described the presence of cannabinoid ligands and receptors on leukocytes and linfóides. It has been shown that tissues was demonstrated that the (endo) cannabinoids are able to modulate the immune system. The best characterized SE receptors CB1 and CB2 are the receivers. CB1 receptors are widely distributed throughout the CNS whereas CB2 receptors, in most cases, are in SI cells. The first was identified endocannabinoid anandamide (AEA) and the second was 2-araquidonilglicerol (2-AG). The AEA is hydrolyzed by fatty acid amide hydrolise (FAAH) and 2-AG is predominantly hydrolyzed by lipase monoacylglycerol (MAGL). To elucidate the role of endocannabinoids as 2-AG and AEA in biological systems are being developed some inhibitors MAGL and FAAH. Among these is the JZL184 (4-nitrophenyl-4- (dibenz [d] [1,3] dioxol-5-yl (hydroxy) methyl) piperidine-1-carboxylate), which inhibits the activity of MAGL. Research reported that JZL184 increases the 2-AG levels without changing of anandamide levels in vitro and in vivo. Among the functions of 2-AG, through the use of JZL184, were the reduction of inflammation in colitis model. A prophylactic treatment with JZL184 exhibits anti-inflammatory and anti-nociceptive effect. Although some previous studies, the role of 2-AG in models of inflammation still lacks depth. The objective of this study is to evaluate the effect of 2-AG using the JZL184 on inflammatory, neuroendocrine and behavioral parameters in a murine model to acute lung injury induced by intranasal administration of LPS.

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)

COSTOLA-DE-SOUZA, CAROLINA; RIBEIRO, ALISON; FERRAZ-DE-PAULA, VIVIANE; CALEFI, ATILIO SERSUN; ARRAIS ALOIA, THIAGO PINHEIRO; GIMENES-JUNIOR, JOAO ANTONIO; DE ALMEIDA, VINICIUS IZIDIO; PINHEIRO, MILENA LOBAO; PALERMO-NETO, JOAO. Monoacylglycerol Lipase (MAGL) Inhibition Attenuates Acute Lung Injury in Mice. PLoS One, v. 8, n. 10, OCT 25 2013. (11/10181-7, 09/51886-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PAVANI, Carolina Costola de Souza. Effects of 2-AG, through monoacylglicerol lipase inhibition, in a murine modelo f acute lung injury LPS-induced. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) São Paulo.