Cannabinoids Affect Dendritic Cell (DC) Potassium Channel Function and Modulate DC T Cell Stimulatory Capacity

Wacnik, Paul W.; Luhr, Katarina M.; Hill, Russell H.; Ljunggren, Hans‐Gustaf; Kristensson, Krister; Svensson, Mattias

doi:10.4049/jimmunol.181.5.3057

Cited by 29 publications

(21 citation statements)

References 62 publications

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“…These findings were consistent with other studies that have shown A -induced I A activation [81,82]. In contrast, CB1 receptor activation has been demonstrated to attenuate the voltage-activated K + currents [83,84].…”

Section: Discussionsupporting

confidence: 83%

CB1 Cannabinoid Receptor Activation Rescues Amyloid ß-Induced Alterations in Behaviour and Intrinsic Electrophysiological Properties of Rat Hippocampal CA1 Pyramidal Neurones

Haghani

Shabani

Javan

et al. 2012

Cell Physiol Biochem

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Background: Amyloid beta (Aβ) is believed to be responsible for the synaptic failure that occurs in Alzheimer′s disease (AD), but there is little known about the functional impact of Aβ on intrinsic neuronal properties. Here, the cellular effect of Aβ-induced neurotoxicity on the electrophysiological properties of CA1 pyramidal neurons and the mechanism(s) of neuroprotection by CB1 cannabinoid receptor activation was explored. Methods: A combination of behavioural, molecular and electrophysiological approaches was used. Results: Bilateral injections of the Aβ peptide fragment (1-42) into the prefrontal cortex caused a significant impairment in the retention and recall capability in the passive avoidance tasks and significantly increased the level of active caspase-3 in the hippocampus. Whole-cell patch clamp recordings revealed a significant reduction in the intrinsic action potential (AP) frequency and an increase in the discharge irregularity in the absence of synaptic inputs in Aβ treated group. Aβ treatment induced also significant changes in both the spontaneous and evoked neuronal responses. However, co-treatment with ACEA, a CB1 receptor agonist, preserved almost the normal intrinsic electrophysiological properties of pyramidal cells. Conclusions: In vivo Aβ treatment altered significantly the intrinsic electrophysiological properties of CA1 pyramidal neurons and the activation of CB1 cannabinoid receptors exerted a strong neuroprotective action against Aβ toxicity.

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Section: Discussionsupporting

confidence: 83%

CB1 Cannabinoid Receptor Activation Rescues Amyloid ß-Induced Alterations in Behaviour and Intrinsic Electrophysiological Properties of Rat Hippocampal CA1 Pyramidal Neurones

Haghani

Shabani

Javan

et al. 2012

Cell Physiol Biochem

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“…15 -17 Cannabinoids reduce the MHC class II expression on the surface of dendritic cells, hence affecting antigen presentation, and inhibit peripheral T-cell activation in response to lipopolysaccharide and anti-CD3 antibodies. 26,29,30 Based on these findings, several studies have focused on the use of cannabinoids for the treatment of immune-mediated diseases, both in experimental models and humans. 29 As the dysregulated proinflammatory response observed in IBD pathogenesis is characterized by a T helper cell type (Th)1 / Th17 immune profile, 31 we explored the influence of endocannabinoids on T cell-mediated gut inflammation, by investigating the in vitro and ex vivo effects of the synthetic non-hydrolysable AEA analog MAEA on proinflammatory cytokine production by anti-CD3 / CD28-stimulated LPMCs, CD3 + LPMCs, and biopsies from inflamed IBD mucosa.…”

Section: Articlesmentioning

confidence: 99%

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

et al. 2011

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Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.[...

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“…MHC molecules are particularly induced upon cell maturation and activation by specific transactivators, the most important of which is MHC class II transactivator CIITA (Reith et al 2005). Very few reports have investigated the role of phyCBs and syCBs on the regulation of MHC expression, yet there is a general consensus that these compounds may reduce MHC molecules either directly (Wacnik et al 2008) or through downregulation of CIITA (Gongora et al 2004). …”

Section: Cannabinoid-mediated Integration Of Brain Immunitymentioning

confidence: 98%

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses

Chiurchiù

Leuti

Maccarrone

2015

J Neuroimmune Pharmacol

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The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells. Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors. In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.

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Cannabinoids Affect Dendritic Cell (DC) Potassium Channel Function and Modulate DC T Cell Stimulatory Capacity

Cited by 29 publications

References 62 publications

CB1 Cannabinoid Receptor Activation Rescues Amyloid ß-Induced Alterations in Behaviour and Intrinsic Electrophysiological Properties of Rat Hippocampal CA1 Pyramidal Neurones

CB1 Cannabinoid Receptor Activation Rescues Amyloid ß-Induced Alterations in Behaviour and Intrinsic Electrophysiological Properties of Rat Hippocampal CA1 Pyramidal Neurones

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses

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