CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia

Tortora, Chiara; Palumbo, Giuseppe; Punzo, Francesca; Argenziano, Maura; Casale, Maddalena; Paola, Alessandra Di; Locatelli, Franco; Perrotta, Silverio

doi:10.3390/ijms20051049

Cited by 18 publications

(43 citation statements)

References 37 publications

(66 reference statements)

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“…They are normally able to inhibit T- and B-cell proliferation [43], whereas in ITP patients, this property is compromised together with their own proliferation [44,45]. It has been observed that the CB2 receptor is more frequently expressed in healthy MSCs than in MSCs obtained from ITP pediatric patients [23] and that a selective stimulation of the cannabinoid receptor can restore the immunomodulatory capabilities of MSCs [46]. Another well-reported aspect in the literature is the capability of AEA and 2-AG to modulate the platelets’ function and survival.…”

Section: The Ec System In Immune Thrombocytopeniamentioning

confidence: 99%

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

Argenziano

Tortora

Bellini

et al. 2019

IJMS

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Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the immune response. They also regulate the inflammatory processes by inhibiting pro-inflammatory mediator release and immune cell proliferation. This review provides an overview on the role of the endocannabinoid system with a major focus on cannabinoid receptors in the pathogenesis and onset of inflammatory and autoimmune pediatric diseases, such as immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity, neuroinflammatory diseases, and type 1 diabetes mellitus. These disorders have a high social impact and represent a burden for the healthcare system, hence the importance of individuating more innovative and effective treatments. The endocannabinoid system could address this need, representing a possible new diagnostic marker and therapeutic target.

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Section: The Ec System In Immune Thrombocytopeniamentioning

confidence: 99%

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

Argenziano

Tortora

Bellini

et al. 2019

IJMS

Self Cite

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“…In particular, mesenchymal stem cells from ITP patients overproduce the pro-inflammatory cytokine IL-6. Regular levels are restored using JWH-133, a selective agonist at CB2 receptors [77]. A proper activation of CB2 receptor reduces the levels of several inflammatory mediators (IL-6, IL-1β and TNF-α) also in animal model of multiple sclerosis [78].…”

Section: Inflammation and Cytokines Productionmentioning

confidence: 99%

Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

Rossi

Tortora

Argenziano

et al. 2020

IJMS

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In late December 2019, a novel coronavirus (SARS-CoV-2 or CoV-19) appeared in Wuhan, China, causing a global pandemic. SARS-CoV-2 causes mild to severe respiratory tract inflammation, often developing into lung fibrosis with thrombosis in pulmonary small vessels and causing even death. COronaVIrus Disease (COVID-19) patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells. Men show higher susceptibility to SARS-CoV-2 infection than women, likely due to estrogens production. The protective role of estrogens, as well as an immune-suppressive activity that limits the excessive inflammation, can be mediated by cannabinoid receptor type 2 (CB2). The role of this receptor in modulating inflammation and immune response is well documented in fact in several settings. The stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells. For these reasons, we hypothesize that CB2 receptor can be a therapeutic target in COVID-19 pandemic emergency.

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“…ITP is characterized by abnormal cytokine secretion, especially by overproduction of pro-inflammatory IL-6 by mesenchymal stem cells. Natural activation of CBR2 or JWH-133 selective agonist implementation reduces IL-6 levels in ITP [ 98 ]. Substitution of glutamine (Q) with arginine (R) at the codon 63 in CBR2 protein changes its polarization and affects receptor–cannabinoid interactions reducing immune modulation function of this receptor [ 99 ].…”

Section: Cannabinoids In Medicinementioning

confidence: 99%

Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases

Śledziński

Nowak-Terpiłowska

Zeyland

2020

IJMS

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Recently, there has been a growing interest in the medical applications of Cannabis plants. They owe their unique properties to a group of secondary metabolites known as phytocannabinoids, which are specific for this genus. Phytocannabinoids, and cannabinoids generally, can interact with cannabinoid receptors being part of the endocannabinoid system present in animals. Over the years a growing body of scientific evidence has been gathered, suggesting that these compounds have therapeutic potential. In this article, we review the classification of cannabinoids, the molecular mechanisms of their interaction with animal cells as well as their potential application in the treatment of human diseases. Specifically, we focus on the research concerning the anticancer potential of cannabinoids in preclinical studies, their possible use in cancer treatment and palliative medicine, as well as their influence on the immune system. We also discuss their potential as therapeutic agents in infectious, autoimmune, and gastrointestinal inflammatory diseases. We postulate that the currently ongoing and future clinical trials should be accompanied by research focused on the cellular and molecular response to cannabinoids and Cannabis extracts, which will ultimately allow us to fully understand the mechanism, potency, and safety profile of cannabinoids as single agents and as complementary drugs.

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CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia

Cited by 18 publications

References 37 publications

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases

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