Cannabinoid Receptors as Regulators of Neutrophil Activity in Inflammatory Diseases

Souza, Mariana C.; Rosas, Elaine Cruz

doi:10.5772/intechopen.81995

Cited by 6 publications

(5 citation statements)

References 103 publications

(109 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cannabinoids modulate several aspects of PMN biology 76 . However, the role of the cannabinoid system on PMN migration is controversial.…”

Section: Discussionmentioning

confidence: 99%

“…However, the role of the cannabinoid system on PMN migration is controversial. Some studies showed that CB activation did not affect PMN migration, whereas other authors demonstrated that CB agonists induced migration of PMNs toward inflammatory stimuli 21,76,77 . Two membrane‐bound glycoproteins (i.e., CD66b and CD62L) regulating their adhesive property are involved in neutrophil migration and activation 37 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

LPS-mediated neutrophil VEGF-A release is modulated by cannabinoid receptor activation

Braile

Cristinziano

Marcella

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Neutrophils (PMNs) are innate immune cells with primary roles in inflammation and in host defense against infections. Both inflammatory and tumor angiogenesis are modulated by a sequential, coordinated production of angiogenic factors such as vascular endothelial growth factors (VEGFs), angiopoietins, hepatocyte growth factor (HGF), and chemokines. These factors are produced by several immune cells, including PMNs. Activation of cannabinoid receptor type-1 (CB 1) and-2 (CB 2) has been suggested as a new strategy to modulate in vitro and in vivo angiogenesis. We sought to investigate whether activation of CB 1 and CB 2 by CB agonists modulate LPS-mediated angiogenic activity of human PMNs. Highly purified PMNs were isolated from buffy coats of healthy donors. Cells were stimulated with CB 1 and CB 2 agonists/antagonists alone and/or in combination with LPS. Angiogenic factors in cell-free supernatants were measured by ELISA. The modulation of activation markers of PMNs by CB agonists was evaluated by flow cytometry. Angiogenesis in vitro was measured as tube formation by optical microscopy. Endothelial cell permeability was assessed by an in vitro vascular permeability assay. LPS-activated PMNs released VEGF-A, CXCL8, and HGF. Preincubation of PMNs with low concentrations of CB 1 and CB 2 agonists inhibited VEGF-A release induced by LPS, but did not affect CXCL8 and HGF production. The effects of CB agonists on VEGF-A release induced by LPS were reversed by preincubation with CB antagonists. CB agonists modulated in vitro angiogenesis and endothelial permeability induced by supernatants of LPS-activated PMNs through the reduction of VEGF-A. Neutrophils play a central role in the control of bacterial infections and in the outcome of sepsis. The latter condition is associated with an increase in circulating levels of VEGF-A. We demonstrated that low concentrations of CB agonists inhibit VEGF-A release from LPS-activated PMNs. These results suggest that CB agonists might represent a novel therapeutic strategy in patients with sepsis.

show abstract

“…Cannabinoids modulate several aspects of PMN biology 76 . However, the role of the cannabinoid system on PMN migration is controversial.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LPS-mediated neutrophil VEGF-A release is modulated by cannabinoid receptor activation

Braile

Cristinziano

Marcella

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Eligible patients were those diagnosed with plaque psoriasis for at least 6 months with lesions affecting at least 10% of total body surface area. The severity of psoriasis was assessed using the Psoriasis Area and Severity Index (PASI) score (median 17; range [13][14][15][16][17][18][19][20][21]. None of the patients or healthy subjects received topical, injectable or oral medications during the 4 weeks before the study.…”

Section: Effects Of Cbd On Apoptosis In Uvb-irradiated Keratinocytesmentioning

confidence: 99%

“…Options for integrative biomedicine treatments combining UV therapy with antiinflammatory compounds seem attractive and aim to eliminate the negative and intensify the positive effects of UV irradiation. Cannabidiol (CBD), a phytocannabinoid that not only has anti-inflammatory properties but also is a powerful antioxidant [15][16][17], seems to be a potentially promising compound for such therapy. CBD has positive effects on psoriatic skin cells [17][18][19] and can protect healthy cells from the negative effects of UV irradiation.…”

Section: Introductionmentioning

confidence: 99%

Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation

Wójcik

Gęgotek

Žarković

2021

IJMS

View full text Add to dashboard Cite

Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ2 level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ2, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.

show abstract

“…Activation of endocannabinoid receptors on immune cells results in a decrease in proinflammatory cytokine release 14 , 15 and reduces the neutrophil and macrophage recruitment. 16 Multicellular damage caused by proinflammatory and pro-oxidative mediators leads to multiple organ dysfunction, worsening of the patient's general medical condition, and finally, death. Considering the role of endocannabinoids, we hypothesized that they could be early predictors of severe events in sepsis.…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications

Šahinović

Mandić

Mihić

et al. 2023

Cannabis and Cannabinoid Research

View full text Add to dashboard Cite

Background: One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years; however, little is known about its role in sepsis in humans. This study aimed to assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality, invasive mechanical ventilation (IMV) requirement, and length of stay (LOS) in patients with sepsis. Materials and Methods: In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, N =53; nonsurvival, N =53), IMV requirement (IMV group, N =26; non-IMV group, N =80), and LOS (LOS <10 days, N =59; LOS ≥10 days, N =47). Patients' clinical status was assessed along with laboratory biomarkers as well as AEA and 2-AG concentration measurements early on admission to emergency units. AEA and 2-AG levels were measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA processor, EtiMax 3000 (DiaSorin, Saluggia, Italy). The predictive value of AEA and 2-AG for the studied sepsis outcomes and complications was analyzed using univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis. Results: Two endocannabinoids showed no significant difference between survivors and nonsurvivors, although an AEA concentration <7.16 μg/L predicted mortality outcome with a sensitivity of 57% (95% confidence interval [CI] 42–71) and specificity of 80% (95% CI 66–91). AEA concentrations ≤17.84 μg/L predicted LOS ≥10 days with sensitivity of 98% (95% CI 89–100) and specificity of 34% (95% CI 22–47). When analyzing IMV requirement, levels of AEA and 2-AG were significantly lower within the IMV group compared with the non-IMV group (5.94 μg/L [2.04–9.44] and 6.70 μg/L [3.50–27.04], p =0.043, and 5.68 μg/L [2.30–8.60] and 9.58 μg/L [4.83–40.05], p =0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% ( p <0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03–183.83; p =0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67–0.93; p =0.004). Conclusion: Low AEA concentration is a prognostic factor of hospital LOS longer than 10 days. Lower AEA and 2-AG concentrations obtained at the time of admission to the hospital are predictors of IMV requirement.

show abstract

Cannabinoid Receptors as Regulators of Neutrophil Activity in Inflammatory Diseases

Cited by 6 publications

References 103 publications

LPS-mediated neutrophil VEGF-A release is modulated by cannabinoid receptor activation

LPS-mediated neutrophil VEGF-A release is modulated by cannabinoid receptor activation

Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation

Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications

Contact Info

Product

Resources

About