Blockade of cannabinoid receptors reduces inflammation, leukocyte accumulation and neovascularization in a model of sponge-induced inflammatory angiogenesis

Guabiraba, Rodrigo; Russo, Remo Castro; Coelho, Amanda M.; Ferreira, Mônica Alves Neves Diniz; Lopes, Gabriel Augusto Oliveira; Gomes, Ariane K. C.; Andrade, Sílvia Passos; Barcelos, Lucíola da Silva; Teixeira, Mauro Martins

doi:10.1007/s00011-013-0638-8

Cited by 23 publications

(21 citation statements)

References 71 publications

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“…Saffron is also endowed with a potent antioxidant activity, that has been attributed primarily to its crocins constituent (see for ref[8]). In line with this, reduction of inflammation due to the downregulation of chemokine CCL2 by saffron [14], and remarkably also by CB 1 /CB 2 antagonists [46], could be a common pattern of response against retinal damage. Indeed, when the retina is damaged by bright light, a variety of pathways are activated, including an upregulation of Chemokin (C-C motif) Ligand 2 (CCL2) which recruits macrophages to scavenge retinal debris.…”

Section: Discussionmentioning

confidence: 81%

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

et al. 2016

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Experimental studies demonstrated that saffron (Crocus sativus) given as a dietary supplement counteracts the effects of bright continuous light (BCL) exposure in the albino rat retina, preserving both morphology and function and probably acting as a regulator of programmed cell death [1]. The purpose of this study was to ascertain whether the neuroprotective effect of saffron on rat retina exposed to BCL is associated with a modulation of the endocannabinoid system (ECS). To this aim, we used eight experimental groups of Sprague-Dawley rats, of which six were exposed to BCL for 24 hours. Following retinal function evaluation, retinas were quickly removed for biochemical and morphological analyses. Rats were either saffron-prefed or intravitreally injected with selective type-1 (CB1) or type-2 (CB2) cannabinoid receptor antagonists before BCL. Prefeeding and intravitreally injections were combined in two experimental groups before BCL. BCL exposure led to enhanced gene and protein expression of retinal CB1 and CB2 without affecting the other ECS elements. This effect of BCL on CB1 and CB2 was reversed by saffron treatment. Selective CB1 and CB2 antagonists reduced photoreceptor death, preserved morphology and visual function of retina, and mitigated the outer nuclear layer (ONL) damage due to BCL. Of interest, CB2-dependent neuroprotection was more pronounced than that conferred by CB1. These data suggest that BCL modulates only distinct ECS elements like CB1 and CB2, and that saffron and cannabinoid receptors could share the same mechanism in order to afford retinal protection.

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Section: Discussionmentioning

confidence: 81%

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

et al. 2016

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“…Additionally, activation of CB2R diminishes the recruitment of neutrophils, T cells and macrophages to the inflamed colon (Storr et al 2009;Singh et al 2012); reduces expression of adhesion molecules in brain endothelium, decreasing leukocyte engagement and recruitment (Ramirez et al 2012); attenuates monocytes adhesion to and migration across of primary human brain microvascular endothelial cells (Rom et al 2013); inhibits Th17 differentiation in experimental autoimmune encephalomyelitis (Kong et al 2014) and liver disease (Kong et al 2014;Guillot et al 2014); inhibits the production of proinflammatory cytokines (IL-1␤, IL-6, IL-8, TNF␣ and IL-17) in splenocytes (Gui et al 2013), in human mesenchymal stromal cells (Rossi et al 2013), and in iris and ciliary body tissue (Toguri et al 2014). Furthermore, activation of CB2R reduces neovascularization in a model of sponge-induced inflammatory angiogenesis (Guabiraba et al 2013), which might be helpful to suppress synovial angiogenesis and pannus formation in RA. However, these mechanisms are waiting to be clarified in RA/CIA treatment with CB2R agonists.…”

Section: Discussionmentioning

confidence: 97%

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis

Gui

Liu

et al. 2015

Immunobiology

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“…The CB1 and CB2 receptors are expressed during inflammatory angiogenesis; CB1 receptor appeared to be strongly involved in leukocyte accumulation and cytokine production, CB2 receptor is mainly linked to a pro-angiogenic response, especially through early neutrophil activation. Double blockade of cannabinoid receptors favored slightly better inhibition of inflammatory angiogenesis [48]. In the skin samples of healthy dogs, CB1 and CB2 receptors immunoreactivity was detected in various types of cells in the epidermis and in cells in the dermis, including perivascular cells with mast cell morphology, fibroblasts, and endothelial cells; in the skin samples of dogs with atopic dermatitis, CB1 and CB2 immunoreactivity was stronger than it was in skin samples of healthy dogs [49].…”

Section: Discussionmentioning

confidence: 99%

Monoacylglycerol Lipase (MAGL) Inhibition Attenuates Acute Lung Injury in Mice

et al. 2013

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Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG), is mediated by monoacylglycerol lipase (MAGL). The piperidine carbamate, 4-nitrophenyl- 4-(dibenzo[d] [1,3]dioxol-5-yl (hydroxy) methyl) piperidine- 1-carboxylate (JZL184), is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p.)) of JZL184, in a murine model of lipopolysaccharide (LPS) -induced acute lung injury (ALI) 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL) and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) and the AM630 selective CB2 receptor antagonist ([6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)-methanone) blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors.

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Blockade of cannabinoid receptors reduces inflammation, leukocyte accumulation and neovascularization in a model of sponge-induced inflammatory angiogenesis

Abstract: Blockade of cannabinoid receptors reduced leukocyte accumulation, inflammation and neovascularization, suggesting an important role of endocannabinoids in sponge-induced inflammatory angiogenesis both via CB1 and CB2 receptors.

Cited by 23 publications

References 71 publications

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis

Monoacylglycerol Lipase (MAGL) Inhibition Attenuates Acute Lung Injury in Mice

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