scholarly journals Characterization of Endocannabinoid System and Interleukin Profiles in Ovine AEC: Cannabinoid Receptors Type-1 and Type-2 as Key Effectors of Pro-Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1008 ◽  
Author(s):  
Luana Greco ◽  
Valentina Russo ◽  
Cinzia Rapino ◽  
Clara Di Germanio ◽  
Filomena Fezza ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Middle Stage ◽  
Selective Agonists ◽  
Anti Inflammatory

Amniotic epithelial cells (AEC) have been proposed as promising clinical candidates for regenerative medicine therapies due to their immunomodulatory capacity. In this context, the endocannabinoid system (ECS) has been identified as mediating the immune-stem cell dialogue, even if no information on AEC is available to date. Therefore, this study was designed to assess whether ECS is involved in tuning the constitutive and lipopolysaccharide (LPS)-induced ovine AEC anti-inflammatory and pro-inflammatory interleukin (IL-10, IL-4, and IL-12) profiles. Firstly, interleukins and ECS expressions were studied at different stages of gestation. Then, the role of cannabinoid receptors 1 and 2 (CB1 and CB2) on interleukin expression and release was investigated in middle stage AEC using selective agonists and antagonists. AEC displayed a degradative more than a synthetic endocannabinoid metabolism during the early and middle stages of gestation. At the middle stage, cannabinoid receptors mediated the balance between pro-inflammatory (IL-12) and anti-inflammatory (IL-4 and IL-10) interleukins. The activation of both receptors mediated an overall pro-inflammatory shift—CB1 reduced the anti-inflammatory and CB2 increased the pro-inflammatory interleukin release, particularly after LPS stimulation. Altogether, these data pave the way for the comprehension of AEC mechanisms tuning immune-modulation, crucial for the development of new AEC-based therapy protocols.

scholarly journals Discovery of Selective Cannabinoid CB2 Receptor Agonists by High-Throughput Screening

2017 ◽  
Vol 23 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Lisa M. Ogawa ◽  
Neil T. Burford ◽  
Yu-Hsien Liao ◽  
Caitlin E. Scott ◽  
Ashley M. Hine ◽  
...  
Keyword(s):  
Side Effects ◽  
High Throughput ◽  
High Throughput Screening ◽  
Immune Modulation ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Allosteric Modulators ◽  
Peripheral Tissues ◽  
Selective Agonists

The endocannabinoid system (ECS) plays a diverse role in human physiology ranging from the regulation of mood and appetite to immune modulation and the response to pain. Drug development that targets the cannabinoid receptors (CB1 and CB2) has been explored; however, success in the clinic has been limited by the psychoactive side effects associated with modulation of the neuronally expressed CB1 that are enriched in the CNS. CB2, however, are expressed in peripheral tissues, primarily in immune cells, and thus development of CB2-selective drugs holds the potential to modulate pain among other indications without eliciting anxiety and other undesirable side effects associated with CB1 activation. As part of a collaborative effort among industry and academic laboratories, we performed a high-throughput screen designed to discover selective agonists or positive allosteric modulators (PAMs) of CB2. Although no CB2 PAMs were identified, 167 CB2 agonists were discovered here, and further characterization of four select compounds revealed two with high selectivity for CB2 versus CB1. These results broaden drug discovery efforts aimed at the ECS and may lead to the development of novel therapies for immune modulation and pain management with improved side effect profiles.

Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor

2014 ◽  
Vol 233 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Valerio Chiurchiù ◽  
Mirko Lanuti ◽  
Giuseppina Catanzaro ◽  
Filomena Fezza ◽  
Cinzia Rapino ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Foam Cells ◽  
Detailed Characterization ◽  
Human Macrophages ◽  
Anti Inflammatory

scholarly journals The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

2019 ◽  
Vol 20 (23) ◽  
pp. 5875 ◽  
Author(s):  
Maura Argenziano ◽  
Chiara Tortora ◽  
Giulia Bellini ◽  
Alessandra Di Paola ◽  
Francesca Punzo ◽  
...  
Keyword(s):  
Social Impact ◽  
Cannabinoid Receptors ◽  
Immune Cell ◽  
Endocannabinoid System ◽  
Pediatric Diseases ◽  
Inflammatory Processes ◽  
Inflammatory Bowel

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.

scholarly journals Possible Role of TGF – B Pathways in Schizophrenia / Moguća Uloga TTGF - B Signalnih Puteva U Shizofreniji

2016 ◽  
Vol 17 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Milica Borovcanin ◽  
Ivan Jovanovic ◽  
Slavica Djukic Dejanovic ◽  
Gordana Radosavljevic ◽  
Nebojsa Arsenijevic ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Psychotic Episode ◽  
T Helper ◽  
Helper Cell Type ◽  
State Marker ◽  
Valuable Marker ◽  
Anti Inflammatory

AbstractThe phenomenological uniqueness of each patient with schizophrenia is determined by complex symptomatology, particularly the overlapping of symptoms and their prominence in certain phases of this mental disorder. Establishing biological markers is an important step in the further objectivisation and quantification of schizophrenia. Identifying the cytokine profiles that precede a psychotic episode could direct the strategies for relapse prevention and be useful in predicting disease progression and treatment response. In the context of infl ammation, TGF-β exerts potent anti-inflammatory and immunosuppressive functions by inhibiting pro-inflammatory cytokine synthesis, but it can also have pro-inflammatory functions through its stimulatory effects on inflammatory Th17 cells. It has been shown that the T helper cell type-1 and type-17 responses are reduced and type-2 response is increased in patients with schizophrenia. Both data from the literature and our results also indicate the presence of an anti-inflammatory response through production of the TGF-β regulatory cytokine. A meta-analysis of plasma cytokine alterations suggested that TGF-β is the state marker for acute exacerbation of schizophrenia, and we showed that TGF-β can also be a valuable marker for psychosis. Hyperactivity of TGF-β signalling pathways in schizophrenia may be both a neuroprotective mechanism and a possible therapeutic target.

scholarly journals Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7693
Author(s):  
Dhanush Haspula ◽  
Michelle A. Clark
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Inflammatory Diseases ◽  
Endocannabinoid System ◽  
Future Directions ◽  
The Past ◽  
Health And Disease ◽  
Made In

The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

scholarly journals Update on the Role of Cannabinoid Receptors after Ischemic Stroke

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Luciano S. A. Capettini ◽  
Silvia Q. Savergnini ◽  
Rafaela F. da Silva ◽  
Nikos Stergiopulos ◽  
Robson A. S. Santos ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cannabinoid Receptors ◽  
Inflammatory Diseases ◽  
Receptor Activation ◽  
Protective Effects ◽  
Peripheral Tissues ◽  
Transmembrane Receptors ◽  
Anti Inflammatory

Cannabinoids are considered as key mediators in the pathophysiology of inflammatory diseases, including atherosclerosis. In particular, they have been shown to reduce the ischemic injury after acute cardiovascular events, such as acute myocardial infarction and ischemic stroke. These protective and anti-inflammatory properties on peripheral tissues and circulating inflammatory have been demonstrated to involve their binding with both selective cannabinoid type 1 (CB1) and type 2 (CB2) transmembrane receptors. On the other hands, the recent discoveries of novel different classes of cannabinoids and receptors have increased the complexity of this system in atherosclerosis. Although only preliminary data have been reported on the activities of novel cannabinoid receptors, several studies have already investigated the role ofCB1andCB2receptors in ischemic stroke. WhileCB1receptor activation has been shown to directly reduce atherosclerotic plaque inflammation, controversial data have been shown on neurotransmission and neuroprotection after stroke. Given its potent anti-inflammatory activities on circulating leukocytes, theCB2activation has been proven to produce protective effects against acute poststroke inflammation. In this paper, we will update evidence on different cannabinoid-triggered avenues to reduce inflammation and neuronal injury in acute ischemic stroke.

103 Characterization of the receptors of the endocannabinoid system in equine sperm: Possible role of anandamide in sperm function

2021 ◽  
Vol 33 (2) ◽  
pp. 159
Author(s):  
C. Arroyo-Salvo ◽  
R. Lottero ◽  
A. Gambini ◽  
S. Perez Martinez
Keyword(s):  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Sperm Capacitation ◽  
Phosphorylated Proteins ◽  
Middle Piece ◽  
Cryopreserved Sperm ◽  
Principal Piece ◽  
Post Hoc

Conventional IVF in horses remains challenging. In particular, stallion sperm fails to penetrate the zona pellucida, possibly due to incomplete invitro sperm capacitation. Therefore, there is a need to elucidate, in horses, molecules with a proven role during capacitation in other mammals. Our laboratory has described the relevance of the endocannabinoid system in capacitation of bovine and murine sperm. We reported that anandamide (AEA), an endocannabinoid present in follicular and oviducal fluids, induced capacitation-associated events. The aims of this work were to characterise the localization of cannabinoid receptors in equine sperm and to evaluate the effects of AEA on levels of tyrosine-phosphorylated proteins (pY) and substrates phosphorylated by protein kinase A (pPKA). Both cannabinoid receptors (CB1, CB2, TRPV1) and pPKA and pY were localised in sperm by indirect immunofluorescence. Sperm (15×106mL−1) were incubated, at 38.5°C in air, in modified Tyrode’s-albumin-lactate-pyruvate (TALP) with 25mM NaHCO3, 5mM dextrose and 1mgmL−1 polyvinyl alcohol (PVA; TALP-Bic-PVA) or TALP-Bic-PVA supplemented with AEA (0.1, 1, 10, 100nM, and 1µM) for 4h. After incubation, Western blot was used to determine levels of pY and pPKA in 4.5×106 sperm. Cryopreserved sperm samples from three stallions were evaluated. The normality of data distributions and homoscedasticity were verified with the Shapiro-Wilk and Levene tests, respectively. Data were analysed by one-way ANOVA and Bonferroni post hoc test, with P<0.05 considered significant. Based on immunofluorescence, CB1 was mainly localised in the post-acrosomal region and flagellum (93.4%±5.5, mean±s.d.), CB2 in the post-acrosomal region and middle piece (89.9%±28.3), and TRPV1 in the post-acrosomal region and flagellum (89.3%±9). Sperm positive for pPKA had fluorescence in the middle piece and principal piece of the flagellum. Incubation with 1nM AEA for 4h induced a 61% increase in pPKA levels compared with TALP-Bic-PVA medium alone, with no induction of pY levels in any treatment. In conclusion, cannabinoid receptors were present in equine sperm, and incubation with AEA induced an increase in PKA activity, an essential event associated with sperm capacitation. To our knowledge, this was the first report describing the presence of receptors of the endocannabinoid system in equine sperm and the potential role of AEA in the acquisition of sperm fertilizing ability.

scholarly journals A Possible Anti-Inflammatory Role of Angiotensin II Type 2 Receptor in Immune-Mediated Glomerulonephritis during Type 1 Receptor Blockade

2006 ◽  
Vol 169 (5) ◽  
pp. 1577-1589 ◽  
Author(s):  
Hirokazu Okada ◽  
Tsutomu Inoue ◽  
Tomohiro Kikuta ◽  
Yusuke Watanabe ◽  
Yoshihiko Kanno ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Blockade ◽  
Immune Mediated ◽  
Anti Inflammatory

scholarly journals Cannabinoid Type-2 Receptor Agonist, JWH133 May Be a Possible Candidate for Targeting Infection, Inflammation, and Immunity in COVID-19

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 285-304
Author(s):  
Niraj Kumar Jha ◽  
Charu Sharma ◽  
Mohamed Fizur Nagoor Meeran ◽  
Saurabh Kumar Jha ◽  
Vivek Dhar Dwivedi ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Endocannabinoid System ◽  
Cb2 Receptor ◽  
Promising Therapeutic Target ◽  
Safety Studies ◽  
Anti Inflammatory ◽  
Preclinical And Clinical Studies

The COVID-19 pandemic, caused by SARS-CoV-2, is a deadly disease affecting millions due to the non-availability of drugs and vaccines. The majority of COVID-19 drugs have been repurposed based on antiviral, immunomodulatory, and antibiotic potential. The pathogenesis and advanced complications with infection involve the immune-inflammatory cascade. Therefore, a therapeutic strategy could reduce infectivity, inflammation, and immune modulation. In recent years, modulating the endocannabinoid system, particularly activation of the cannabinoid type 2 (CB2) receptor is a promising therapeutic target for modulation of immune-inflammatory responses. JWH133, a selective, full functional agonist of the CB2 receptor, has been extensively studied for its potent anti-inflammatory, antiviral, and immunomodulatory properties. JWH133 modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. In this study, we propose that JWH133 could be a promising candidate for targeting infection, immunity, and inflammation in COVID-19, due to its pharmacological and molecular mechanisms in numerous preclinical efficacy and safety studies, along with its immunomodulatory, anti-inflammatory, organoprotective, and antiviral properties. Thus, JWH133 should be investigated in preclinical and clinical studies for its potential as an agent or adjuvant with other agents for its effect on viremia, infectivity, immune modulation, resolution of inflammation, reduction in severity, and progression of complications in COVID-19. JWH133 is devoid of psychotropic effects due to CB2 receptor selectivity, has negligible toxicity, good bioavailability and druggable properties, including pharmacokinetic and physicochemical effects. We believe that JWH133 could be a promising drug and may inspire further studies for an evidence-based approach against COVID-19.

scholarly journals Role of endocannabinoid system in the pathogenesis of obesity: how can we help a patient? From theory to practice

2020 ◽  
Vol 4 (6) ◽  
pp. 382-389
Author(s):  
V.A. Dudareva ◽  
◽  
M.L. Maksimov ◽  
I.G. Djadikova ◽  
A.A. Zveginceva ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Medical Society ◽  
Cannabinoid Receptor 1 ◽  
Peripheral Tissues ◽  
Theory To Practice

Obesity that results in various metabolic disorders is one of the central concerns of modern healthcare system. Only 4% to 5% of patients with metabolic syndrome achieve favorable outcomes without any additional pharmacotherapy. Therefore, many patients require weight-loss drugs in addition to non-pharmacological treatments. The endocannabinoid system and the drugs that affect its functions receive a widespread attention of medical society due to its effects on behavioral and cerebral functions and its potential use as a therapeutic “target” in various peripheral and neurological psychiatric disorders. Among known to date cannabinoid receptors, type 1 receptors play a role in the development of obesity. It was demonstrated that the blockade of these receptors in the hypothalamus reduces appetite, inhibits adipocyte activation in peripheral tissues, prevents lipogenesis, and increases the level of adiponectin. The result is the decreased levels of atherogenic lipoproteins and improved insulin resistance. This article addresses the results of fundamental and clinical studies on Dietressa, a drug composed of affine-purified antibodies to cannabinoid receptor 1. Case report of a patient with obesity that analyzes pharmaceutical and non-pharmaceutical treatment approaches is described.KEYWORDS: obesity, metabolic syndrome, diet, endocannabinoid system, cannabinoids, cannabinoid receptors, affine-purified antibodies.FOR CITATION: Dudareva V.A., Maksimov M.L., Djadikova I.G. et al. Role of endocannabinoid system in the pathogenesis of obesity: how can we help a patient? From theory to practice. Russian Medical Inquiry. 2020;4(6):382–389. DOI: 10.32364/2587-6821-2020-4-6-382-389.

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