“Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer. This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs. This review argues that development and testing of peripherally-acting, tumour-, Cnr2-selective ligands in preclinical models of metastatic cancer will pave the way for future research that will advance our knowledge about the basic mechanism(s) by which the endocannabinoid system regulate cancer metastasis, stimulate the development of a safer cannabis-based therapy for the treatment of cancer and provide policy makers with powerful tools to assess the science and therapeutic potential of cannabinoid-based therapy. Thus, offering the prospect of identifying selective Cnr2 ligands, as novel, alternative to cannabis herbal extracts for the treatment of advanced cancer patients.” https://www.ncbi.nlm.nih.gov/pubmed/28274851]]>
Tag Archives: CB2
Inflammatory Regulation by Driving Microglial M2 Polarization: Neuroprotective Effects of Cannabinoid Receptor-2 Activation in Intracerebral Hemorrhage.
“The cannabinoid receptor-2 (CB2R) was initially thought to be the “peripheral cannabinoid receptor.” Recent studies, however, have documented CB2R expression in the brain in both glial and neuronal cells, and increasing evidence suggests an important role for CB2R in the central nervous system inflammatory response.
Intracerebral hemorrhage (ICH), which occurs when a diseased cerebral vessel ruptures, accounts for 10-15% of all strokes. Although surgical techniques have significantly advanced in the past two decades, ICH continues to have a high mortality rate.
The aim of this study was to investigate the therapeutic effects of CB2R stimulation in acute phase after experimental ICH in rats and its related mechanisms.
These findings demonstrated that CB2R stimulation significantly protected the brain damage and suppressed neuroinflammation by promoting the acquisition of microglial M2 phenotype in acute stage after ICH.
Taken together, this study provided mechanism insight into neuroprotective effects by CB2R stimulation after ICH.”
CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.
“The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. Our results indicate that CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.” https://www.ncbi.nlm.nih.gov/pubmed/28253997]]>
Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis.
“Cannabinoids (CBs) evoke their effects by activating the cannabinoid receptor subtypes CB1-r and CB2-r and exert anti-inflammatory effects altering chemokine and cytokine expression. Various cytokines and chemokines are produced and released by rodent pancreatic acini in acute pancreatitis. Although CB1-r and CB2-r expressed in rat exocrine pancreatic acinar cells do not modulate digestive enzyme release, whether they modulate inflammatory mediators remains unclear. We investigated the CB-r system role on exocrine pancreas in unstimulated conditions and during acute pancreatitis. These findings provide new evidence showing that the pancreatic CB1-r/CB2-r system modulates pro-inflammatory factor levels in rat exocrine pancreatic acinar cells. The dual, time-dependent WIN55,212-induced changes in the development and course of acute pancreatitis support the idea that the role of the endogenous CB receptor system differs according to the local inflammatory status.” https://www.ncbi.nlm.nih.gov/pubmed/20659297]]>
Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells
“Acute pancreatitis is an inflammatory disease, which has several causes and symptoms and requires immediate medical attention. The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor that, in humans, is encoded by the CNR2 gene. CB2Rs are predominantly expressed in the periphery, especially in immune cells, suggesting that CB2R mediates the effects of cannabinoids mainly in the immune system. Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. These results suggest that a CB2R agonist may serve as a novel therapeutic strategy to prevent and/or treat acute pancreatitis. This conclusion is consistent with previous report that a CB2R agonist exhibits a protective effect on pathogenesis in an acute pancreatitis animal model. Our data showing a reduction of intracellular Ca2+ signaling by GW also provide a new target to interpret the role of CB2R agonists in treating acute pancreatitis in addition to CB2R-mediated anti-inflammation.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949433/]]>
Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms.
“The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB(1)) and 2 (CB(2)).
These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH(2)-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines.
Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases.
The unselective CB(1)/CB(2) agonist HU210 ameliorated pancreatitis in wild-type and CB(1)-/- mice, indicating that this effect is mediated by CB(2).
Furthermore, blockade of CB(2), not CB(1), with selective antagonists engraved pathology.
Stimulation with a selective CB(2) agonist attenuated acute pancreatitis and an increased activation of p38 was observed in the acini.
With use of MK2-/- mice, it could be demonstrated that this attenuation is dependent on MK2. Hence, using the MK2-/- mouse model we reveal a novel CB(2)-activated and MAP kinase-dependent pathway that modulates cytokine expression and reduces pancreatic injury and affiliated complications.”
https://www.ncbi.nlm.nih.gov/pubmed/23139224
“Alzheimer’s disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR-139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.”