The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages

Hao, Mingxiu; Jiang, Lingjun; Fang, Ningyuan; Pu, Jun; Hu, Liuhua; Shen, Linghong; Song, Wei; He, Ben

doi:10.1194/jlr.m001511

Cited by 38 publications

(33 citation statements)

References 43 publications

(46 reference statements)

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“…CB 2 receptor activation inhibits the production and release of pro-inflammatory and pro-nociceptive mediators, such as reactive oxygen species (89) and cytokines (87) . In addition, metabolism of 2-AG produces arachidonic acid, a key precursor of pro-inflammatory PG, and disruption of 2-AG hydrolysis reduces the available pool of arachidonic acid and thus reduces inflammation (90) .…”

Section: Peripheral Mechanismsmentioning

confidence: 99%

Endocannabinoid system and pain: an introduction

Burston

Woodhams

2013

Proc. Nutr. Soc.

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The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS. The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated. To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia. Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states. The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states. Pain: Endocannabinoid: AnalgesiaFrom an evolutionary standpoint, pain can be considered a necessary evil, providing a potent warning system to protect an individual from present and future harm. However, not all pain is part of this adaptive response, e.g. persistent pain after injury healing (chronic pain) or pain arising from damage to nerve tissue (neuropathic pain). Pain is the most common complaint in those seeking a physician, and a recent study suggests that pain represents the greatest economic burden of any pathological condition in the USA, with an estimated annual cost of $565-635 billion (1) . Many chronic pain states are refractory to standard analgesics, and even in those which do respond, pain control can be incomplete or only short-term in nature. Of the imperfect currently available analgesics, the most efficacious are the opioids which exploit an endogenous pain control pathway within the central nervous system. However, opioids have significant issues with tolerance, dependence, respiratory depression and opioid-induced hyperalgesia (2) . Over the past few decades, the existence of a second endogenous anti-nociceptive pathway has been revealed: the endocannabinoid (EC) system. *Corresponding author: J. J. Burston, fax +44 (0)115 823 0142, email james.burston@nottingham.ac.uk Abbreviations: 2-AG, 2-arachidonoylglycerol; ACC, anterior cingulate cortex; AEA, anandamide; CB 1 , cannab...

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Section: Peripheral Mechanismsmentioning

confidence: 99%

Endocannabinoid system and pain: an introduction

Burston

Woodhams

2013

Proc. Nutr. Soc.

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“…This results in a change from immune tolerance to immune activation [41][42][43]. Pro-inflammatory cytokines are known to alter the barrier function [39,40], thus forming a vicious circle where increased inflammation leads to a further increase in intestinal permeability. In monolayers of Caco-2 cells, a model of the intestinal epithelial barrier, application of EDTA, pro-inflammatory cytokines, or LPS increases permeability as measured by a decrease in trans-epithelial…”

Section: Box 1 Inflammatory Bowel Diseasesmentioning

confidence: 99%

“…The beneficial effects of increased anandamide levels are CB 1 -and CB 2 -dependent because URB597 and VDM11 had no effect in CB 1 À/À or CB 2 À/À mice [55]. In addition, a newly described FAAH inhibitor, compound (39) in [67] (10 mg/kg, q.d. ), also reduced inflammation in TNBS-colitis, although its effects on anandamide levels or FAAH activity in vivo were not reported [67].…”

Section: Trends In Molecular Medicinementioning

confidence: 99%

“…Indeed, cannabinoids such as anandamide, noladin ether, and arachidonoylcyclopropylamide (ACPA) induce wound-closure in human colonic epithelial cell lines, suggesting that delayed wound healing, a feature of IBD lesions, might be reversed by cannabinoids [34]. Additionally, in vitro studies suggest roles for both cannabinoid receptors in modulating inflammatory processes, including suppression of the activation of macrophages and mast cells, secretion of proinflammatory cytokines, and modulation of T helper lymphocytes by reducing the activated T cell population, inducing their apoptosis, and inhibiting their proliferation [33,[35][36][37][38][39][40].…”

Section: Box 1 Inflammatory Bowel Diseasesmentioning

confidence: 99%

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The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

Alhouayek

Muccioli

2012

Trends in Molecular Medicine

119

100

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“…Using a panel of synthetic cannabinoids, phytocannabinoids, and eCBs, we found that the synthetic cannabinoid WIN55,212-2 and the eCB NADA have the ability to dampen the activation of primary human lung microvascular ECs (HMVEC-lung) by a variety of inflammatory agonists, including bacterial lipopeptides (TLR2 agonist), lipopolysaccharide (LPS) (TLR4 agonist), and TNF␣. Although the anti-inflammatory properties of WIN55,212-2 have previously been described, only a few reports have described the physiological functions of NADA, including its role in inflammation (16,(25)(26)(27)(28)(29)(30)(31)(32).…”

mentioning

confidence: 99%

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

Wilhelmsen

Khakpour

Tran

et al. 2014

Journal of Biological Chemistry

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Background:The endothelium is centrally involved in acute inflammatory disorders. Results: WIN55,212-2 and the endocannabinoid N-arachidonoyl dopamine (NADA), but not anandamide nor 2-arachidonoylglycerol, reduce endothelial activation by bacterial Toll-like receptor agonists and TNF␣. Conclusion: NADA is a newly identified endogenous regulator of endothelial inflammation. Significance: The endothelial endocannabinoid system represents a novel immune regulatory system that could be exploited therapeutically.

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The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages

Cited by 38 publications

References 43 publications

Endocannabinoid system and pain: an introduction

Endocannabinoid system and pain: an introduction

The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

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