Tag Archives: CB2

Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced immunoglobulin IgM secretion.

Posted on by

“Cannabinoid receptor 2 (CB2) is expressed predominantly in the immune system, particularly in plasma cells, raising the possibility that targeting the CB2 pathway could yield an immunomodulatory effect.

Although the role of CB2 in mediating immunoglobulin class switching has been reported, the effects of targeting the CB2 pathway on immunoglobulin secretion per se remain unclear…

These results uncover a novel function of CB2 antagonists and suggest that CB2 ligands may be potential modulators of immunoglobulin secretion.”

Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders.

Posted on by

Publication cover image

“Immune system responsiveness results from numerous factors, including endogenous cannabinoid signaling in immunocytes termed the “immunocannabinoid” system. This system can be an important signaling pathway for immune modulation.

To assess the immunomodulating role of the cannabinoid 2 (CB2) receptor, we sought polymorphisms in the human gene, identified a common dinucleotide polymorphism, and investigated its effect on endocannabinoid-induced inhibition of T lymphocyte proliferation.

Collectively, these results demonstrate reduced endogenous fatty acid amide immunomodulatory responses in individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene variation may be a risk factor for autoimmunity.

The results also support the proposition that the CB2 receptor may represent a novel pharmacological target for selective agonists designed to suppress autoreactive immune responses”

https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0205111

https://www.ncbi.nlm.nih.gov/pubmed/15845647

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

Posted on by

“The cannabinoid system consists of cannabinoid receptors and their ligands, including endocannabinoids, synthetic cannabinoid receptor agonists and antagonists, and phytocannabinoids.

Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and autoimmune disease and CNS injury models results in significant attenuation of clinical disease, and reduction of inflammatory mediators.

…cannabinoids contribute to resolve acute inflammation and to reestablish homeostasis.

Selective CB2R agonists might be valuable future therapeutic agents for the treatment of chronic inflammatory conditions by targeting activated immune cells, including DCs.

Because of their anti-inflammatory functions targeting various immune cells, CB2R agonists could represent valuable therapeutic agents for the treatment of chronic inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488886/

Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation.

Posted on by

Figure 2

“The cannabinoids are a group of terpenophenolic compounds present in the marijuana plant, Cannabis sativa. At present, three general types of cannabinoids have been identified: phytocannabinoids present uniquely in the cannabis plant, endogenous cannabinoids produced in humans and animals, and synthetic cannabinoids generated in a laboratory. It is worth noting that Cannabis sativa produces over 80 cannabinoids…

An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions.

…there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer’sdisease to name a few), mainly mediated by CB(2) activation.

This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

The full potential of CB2 agonists as therapeutic agents remains to be realized.

Despite some inadequacies of preclinical models to predict clinical efficacy in humans and differences between the signaling of human and rodent CB2 receptors, the development of selective CB2 agonists may open new avenues in therapeutic intervention.

Such interventions would aim at reducing the release of pro-inflammatory mediators particularly in chronic neuropathologic conditions such as HAND or MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663904/

 

Targeting the cannabinoid pathway limits the development of fibrosis and autoimmunity in a mouse model of systemic sclerosis.

Posted on by

Figure 1

“Our aim was to evaluate the roles of the cannabinoid pathway in the induction and propagation of systemic sclerosis (SSc) in a mouse model…

Experiments performed in CB2-deficient mice confirmed the influence of CB2 in the development of systemic fibrosis and autoimmunity. Therefore, we demonstrate that the CB2 receptor is a potential target for the treatment of SSc because it controls both skin fibroblast proliferation and the autoimmune reaction.

In this report, we demonstrate for the first time the highly protective role of cannabinoid agonists in SSc. Because these agonists are available and well-tolerated under clinical conditions, our data offer a new therapeutic opportunity in this life-threatening disease.

In conclusion, modulation of the endocannabinoid system is a novel approach for the treatment of various inflammatory diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893662/

Targeting the CB2 receptor for immune modulation.

Posted on by

“Early work on the biology of the components of Cannabis sativa showed evidence for a potential influence on immune regulation.

With the discovery of a peripheral cannabinoid receptor associated with immune cells, many laboratories have sought to link the immunoregulatory activities of cannabinoid compounds with this receptor, hoping that such compounds would lack the psychoactive effects of marijuana and other nonspecific cannabinoid agonists.

In this report, the authors investigate the role of the cannabinoid CB2 receptor in immune regulation, with particular emphasis on compounds shown to regulate immune cell recruitment.

The authors conclude by using the immune cell recruitment model to rationalise cannabinoidCB2 receptor-specific effects in modulating immune disease, particularly the increasing evidence for its role in experimental autoimmuneencephalomyelitis and in influencing bone density.”

http://www.ncbi.nlm.nih.gov/pubmed/16981823

Updating the chemistry and biology of cannabinoid CB2 receptor-specific inverse agonists.

Posted on by

“The cannabinoid CB(2) receptor continues to be an intriguing target for the potential therapeutic benefit of cannabinoids. Because this receptor is significantly found outside the brain, compounds specific for the CB(2) receptor may be free of the side effects that have plagued cannabinoid CB(1) receptor-based therapeutics.

In this review, we will discuss a class of compounds which modulate the constitutive activity of the cannabinoid CB(2) receptor, the inverse agonists. We will discuss recent chemical advances that provide new compounds to investigate the biology based on this pharmacology. We will then discuss new biology associated with the cannabinoid CB(2) receptor for hints of how these compounds can best be utilized in vivo.”

http://www.ncbi.nlm.nih.gov/pubmed/20370714

Biology and therapeutic potential of cannabinoid CB2 receptor inverse agonists

Posted on by

Figure 2

“Evidence has emerged suggesting a role for the cannabinoid CB2 receptor in immune cell motility. This provides a rationale for a novel and generalized immunoregulatory role for cannabinoid CB2 receptor-specific compounds…

An ability to control the migration of inflammatory cells to the site of insult is a powerful strategy for the development of immunomodulators. Our work on triaryl bis-sulphones suggest that the cannabinoid CB2 receptor-specific inverse agonists may serve as such immune modulators…

Further studies, using these and other CB2 receptor-specific compounds, will be required to resolve the complex pharmacology of cannabinoids and the cannabinoid CB2 receptor, and to determine the most effective pharmacology to exploit this therapeutic target.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219522/

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: potential role for CB2-selective ligands as immunosuppressive agents.

Posted on by

“Marijuana has been used for recreational and medicinal purposes for centuries. Its medicinal use can be traced back to ancient Chinese and Egyptian civilizations…

Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties…

The current study suggests that targeting CB2 receptors may constitute a unique treatment modality against inflammatory diseases…

Together, this study suggests that CB2-selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1864948/

Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.

Posted on by

“The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis.

Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity…

Together, our results demonstrate that the cannabinoid system within the CNS plays a critical role in regulating autoimmune inflammation, with the CNS directly suppressing T-cell effector function via the CB(2) receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/17401376