WIN55,212-2-Mediated Inhibition of HIV-1 Expression in Microglial Cells: Involvement of Cannabinoid Receptors

Rock, R. Bryan; Gekker, Genya; Hu, Shuxian; Sheng, Wen S.; Cabral, Guy A.; Martin, Billy R.; Peterson, Phillip K.

doi:10.1007/s11481-006-9040-4

Cited by 49 publications

(44 citation statements)

References 20 publications

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“…Esposito et al (2002) reported that activation of the CB 1 receptor protects rat glioma cells from nitric oxide-mediated cell toxicity induced by the Tat protein. Rock et al (2007) showed that the CB 2 receptor is involved in cannabinoid-mediated inhibition of viral replication in microglial cell cultures and that cannabinoids down-regulate the HIV-1 coreceptor CCR5. Cannabinoid agonists also have been reported to significantly decrease the permeability of human brain microvascular endothelial cells induced by the HIV-1 envelope glycoprotein Gp120 by preventing the down-regulation of the tight junction proteins, claudin-5 and zonula occludens-1 (Lu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports indicate that cannabinoids inhibit viral expression and downregulate CC chemokine receptor 5 (CCR5), a chemokine receptor that is a coreceptor for HIV-1 entry (Rock et al, 2007). In addition, cannabinoid receptor agonists have been reported to decrease significantly the permeability of human brain microvascular endothelial cells induced by Gp120 by preventing the down-regulation of integral tight junction proteins (Lu et al, 2008).…”

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confidence: 99%

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Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB₂Cannabinoid Receptor

Raborn

Cabral

2010

J Pharmacol Exp Ther

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Macrophages and macrophage-like cells are important targets of HIV-1 infection at peripheral sites and in the central nervous system. After infection, these cells secrete a plethora of toxic factors, including the viral regulatory trans-activating protein (Tat). This protein is highly immunogenic and also serves as a potent chemoattractant for monocytes. In the present study, the exogenous cannabinoids ␦-9-tetrahydrocannabinol (THC) and (Ϫ)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP55940) were shown to significantly inhibit migration of human U937 macrophage-like cells to the Tat protein in a concentration-related manner. The CB 1 receptor-selective agonist N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA) had no effect on Tat-mediated migration. In contrast, the CB 2 receptor-selective agonist (1R,3R)-1-[4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl]-3-methylcyclohexanol (O-2137) exerted a concentration-related inhibition of U937 cell migration in response to Tat. Pharmacological blockage of CB 1 receptor signaling using the antagonist 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(1-piperidyl)pyrazole-3-carboxamide hydrochloride (SR141716A) had no effect on CP55940-mediated inhibition of macrophage migration to Tat, whereas treatment with the CB 2 receptor antagonist (1S-endo)-5-(4-chloro-3-methylphenyl)-1-((4-methylphenyl)methyl)-N-(1,3,3-trimethylbicyclo(2.2.1)hept-2-yl)-1H-pyrazole-3-carboxamide (SR144528) reversed the CP55940-mediated inhibition of migration. In addition, THC had no inhibitory effect on U937 migration to Tat after small interfering RNA knockdown of the CB 2 receptor. Collectively, the pharmacological and biochemical knockdown data indicate that cannabinoid-mediated modulation of macrophage migration to the HIV-1 Tat protein is linked to the CB 2 cannabinoid receptor. Furthermore, these results suggest that the CB 2 cannabinoid receptor has potential to serve as a therapeutic target for ablation of HIV-1-associated untoward inflammatory response.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB₂Cannabinoid Receptor

Raborn

Cabral

2010

J Pharmacol Exp Ther

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“…Cannabinoids may also modulate the activity of TRPV1, TRPA1, and TRPM8 channels by a yet unknown mechanism (196). Rodent microglial cells in vitro express CB 1 and CB 2 cannabinoid receptors as well as the third, not yet cloned, receptor (114,259,744,766). The constitutive expression of cannabinoid receptors in the resting microglia is very low, if at all existing.…”

Section: E Cannabinoid Receptorsmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,144

2,981

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Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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“…Glial cells involved in mediating inflammatory processes are resident within the spinal cord and include both astroglia and microglia, the latter of which has been directly implicated in the initiation of peripheral injury-induced pain [12]. Moreover, microglia have been shown to express cannabinoid receptors [13][14][15][16], and to produce and inactivate endocannabinoids [15,17,18].…”

Section: Introductionmentioning

confidence: 99%

Role of Endocannabinoids in Neuron-Glial Crosstalk

Luongo¹,

Palazzo²,

Novellis³

et al. 2010

TOPAINJ

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Evidence shows bidirectional crosstalk between neurons and glia, suggesting that glia play an active role in synaptic plasticity leading to chronic pain. Importantly, gliosis has been implicated in the development and maintenance of hyperalgesia or allodynia following chronic inflammation or nerve injury. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG), or the lipoamino acid N-arachydonoyldopamine (NADA), are fatty acid derivative neurotransmitters, named endocannabinoids (eCBs). These perform several biological actions, via the activation of cannabinoid type 1 and 2 (CB1/CB2) receptors belonging to the G-protein-coupled receptor family. The eCBs are produced on demand by neurons or glial cells and it has been suggested that they might be involved in the crosstalk between astrocytes, microglia, oligodendrocytes and neurons. In chronic pain, the modified glial or neural activity also seems to be associated with changes in eCB levels in pain processing areas either in the spinal cord or the brain. The activation of the eCB system in microglia or astrocytes could be crucial in modulating axonal growth and synaptogenesis at the base of neural phenotypic changes. Furthermore, changes in eCBs levels have been suggested to affect the destiny of cells: death or survival may depend on a specific pain condition. Thus, although eCBs are emerging as neurotransmitters responsible for the regulation of glia-neuron crosstalk in chronic pain, the precise mechanisms leading to eCB production, the origin and the timecourse of eCB release, the eCB release switch from one cell type to the other and their movement or catabolism across the glial or neural cell membrane nevertheless still remain unknown. These issues together with alternative eCB targets will be addressed in the current review.

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WIN55,212-2-Mediated Inhibition of HIV-1 Expression in Microglial Cells: Involvement of Cannabinoid Receptors

Cited by 49 publications

References 20 publications

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB₂Cannabinoid Receptor

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB₂Cannabinoid Receptor

Physiology of Microglia

Role of Endocannabinoids in Neuron-Glial Crosstalk

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WIN55,212-2-Mediated Inhibition of HIV-1 Expression in Microglial Cells: Involvement of Cannabinoid Receptors

Cited by 49 publications

References 20 publications

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB2Cannabinoid Receptor

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB2Cannabinoid Receptor

Physiology of Microglia

Role of Endocannabinoids in Neuron-Glial Crosstalk

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Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB₂Cannabinoid Receptor

Cannabinoid Inhibition of Macrophage Migration to the Trans-Activating (Tat) Protein of HIV-1 Is Linked to the CB₂Cannabinoid Receptor