“Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.”
Tag Archives: CB2
CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.
“Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens.
Here we examined the role of CB(2) receptors in regulating the host’s response to sepsis…
Taken together, our results establish for the first time that CB(2) receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2) receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.”
The cannabinoid receptor 2 is critical for the host response to sepsis.
“These data suggest that CB2R is a critical regulator of the immune response to sepsis and may be a novel therapeutic target.”
Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and systemic inflammatory mediator release in acute experimental sepsis.
“The aim of this study was to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models…
CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.”
The cannabinoid 2 receptor as a potential therapeutic target for sepsis.
“The sepsis syndrome represents an improper immune response to pathogens and is associated with an unacceptably high rate of mortality. Although supportive care is of benefit to the septic patient, there are no viable therapeutics available that target the immune system suitable for the whole septic population. Recently, using a physiologically relevant murine mouse model, the cannabiniod 2 receptor has been shown to play a critical role in the host response to sepsis. Here, the structure, expression, signaling, and function of the CB2 receptor on leukocytes will be reviewed. Further, the effects mediated by the CB2 receptor during sepsis will be reviewed. Altogether, alterations in inflammation and the host response during sepsis by the CB2 receptor support its use as a possible therapeutic agent.”
Experimental cannabinoid 2 receptor-mediated immune modulation in sepsis.
“Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics.
The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model.
Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.”
Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver.
“Interleukin (IL)-17 is a proinflammatory and fibrogenic cytokine mainly produced by T-helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL-22.
Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti-inflammatory and antifibrogenic effects.
In the present study, we further investigated the mechanism underlying antifibrogenic properties of CB2 receptor and explored its effect on the profibrogenic properties of IL-17.
These data demonstrate that CB2 receptor activation decreases liver fibrosis by selectively reducing IL-17 production by Th17 lymphocytes via a STAT5-dependent pathway, and by blunting the proinflammatory effects of IL-17 on its target cells, while preserving IL-22 production.”
Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.
“The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993 while looking for an alternative receptor that could explain the pharmacological properties of Δ(9)-tetrahydrocannabinol.
CB2 was identified among cDNAs based on its similarity in amino acid sequence to the CB1receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.
In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, peripheral nervous system, and gastrointestinal tract.
Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain, and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.
Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this Perspective, we seek to provide a concise update of progress in the field.”
CB2 cannabinoid receptor mediation of antinociception.
“Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects.
The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception…
The CB2 receptor-selective agonist produces antinociceptive… activation of CB2 receptors results in antinociception…
…confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain.”
Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors.
“The efficacy of cannabinoids against high-grade glioma in animal models, mediated by two specific receptors, CB1 and CB2, raised promises for targeted treatment of the most frequent and malignant primary brain tumors.
Unlike the abundantly expressed CB1, the CB2 receptor shows a restricted distribution in normal brain. Although brain tumors constitute the second most common malignancy in children and the prevalence of histological types of brain tumors vary significantly between the adult and pediatric populations, cannabinoid receptor expression in pediatric tumors remains unknown.
In the present study, we compared the expression of the CB2 receptor in paraffin-embedded sections from primary brain tumors of adult and pediatric patients. Most glioblastomas expressed very high levels of CB2 receptors and the expression correlated with tumor grade.
Interestingly, some benign pediatric astrocytic tumors, such as subependymal giant cell astrocytoma (SEGA), which may occasionally cause mortality owing to progressive growth, also displayed high CB2 immunoreactivity.
The high levels of CB2 expression would predestine those tumors to be vulnerable to cannabinoid treatment.
In contrast, all examined cases of embryonal tumors (medulloblastoma and S-PNET), the most frequently diagnosed malignant brain tumors in childhood, showed no or trace CB2 immunoreactivity.
Our results suggest that the CB2 receptor expression depends primarily on the histopathological origin of the brain tumor cells and differentiation state, reflecting the tumor grade.”