Endocannabinoids limit excessive mast cell maturation and activation in human skin

Sugawara, Koji; Bı́ró, Tamás; Tsuruta, Daisuke; Tóth, Balázs István; Kromminga, Arno; Zákány, Nóra; Zimmer, Anne; Funk, Wolfgang; Gibbs, Bernhard F.; Zimmer, Andreas; Paus, Ralf

doi:10.1016/j.jaci.2011.11.009

Cited by 120 publications

(176 citation statements)

References 64 publications

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“…Endocannabinoids, by activating CB1 receptors, are able to limit the excessive number and the activation of mast cells in allergic diseases that in turn may be due to insufficient CB1 stimulation (829). In an animal models of allergic contact dermatitis, skin 2-AG levels are elevated and the treatment with a CB2 antagonist attenuates both the recruitment of eosinophils and the swelling in the challenged zone (639), whereas allergic inflammation is suppressed by ablation of CB2 (571).…”

Section: Skinmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

366

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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Section: Skinmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

366

337

View full text Add to dashboard Cite

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“…120 During the past year, there have also been several new insights into potential mechanisms by which pruritus and mast cell activation can be controlled in patients with AD. 121,122 Urticaria and angioedema Mortality in patients with hereditary angioedema was often due to laryngeal attacks in previous undiagnosed patients. 123 Generalized urticaria after vaccination with helminth antigens 124 attracted interest this past year.…”

Section: Treatment Of Admentioning

confidence: 99%

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012

Sicherer

Leung

2013

Journal of Allergy and Clinical Immunology

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This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2012. Studies support an increase in peanut allergy prevalence in children and exposure to the antibacterial agent triclosan and having filaggrin (FLG) loss-of-function mutations as risk factors for food sensitization. The role of specific foods in causing eosinophilic esophagitis is elucidated by several studies, and microRNA analysis is identified as a possible noninvasive disease biomarker. Studies on food allergy diagnosis emphasize the utility of component testing and the possibility of improved diagnosis through stepped approaches, epitope-binding analysis, and bioinformatics. Treatment studies of food allergy show promise for oral immunotherapy, but tolerance induction remains elusive, and additional therapies are under study. Studies on anaphylaxis suggest an important role for platelet-activating factor and its relationship to the need for prompt treatment with epinephrine. Insights on the pathophysiology and diagnosis of non-IgE-mediated drug allergy are offered, with novel data regarding the interaction of drugs with HLA molecules. Numerous studies support influenza vaccination of persons with egg allergy using modest precautions. Evidence continues to mount that there is cross-talk between skin barrier defects and immune responses in patients with atopic dermatitis. Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease.

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“…N 1 -MeSpd also selectively stimulated expression of the epithelial stem cell-associated keratin, K15, but not K19, and exerted both anti-inflammatory and anti-oxidant effects on cultured human KCs. Theoretically, the anti-inflammatory effects of N 1 -MeSpd as observed in our study could also be mediated in part by effects on macrophages and mast cells [5], which are present in the mesenchyme of the human HF and take part in different aspects of its normal growth and function [20].…”

Section: Discussionmentioning

confidence: 55%

N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

et al. 2015

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Spermidine (Spd), the prototypic polyamine, has been shown to be essential for hair follicle (HF) growth. However, Spd can be readily converted into other polyamines, and is physiologically unstable. Therefore, to assess its individual functions on HFs, we used the metabolically stable Spd analog N(1)-methylspermidine (N(1)-MeSpd). N(1)-MeSpd was confirmed to be a metabolically stable compound, with a half life of 90 h. 0.5 µM N(1)-MeSpd strongly prolonged anagen and decreased cell apoptosis in HFs in culture after 6 days, accompanied by specific stimulation of the expression of the epithelial stem cell-associated keratin, K15. N(1)-MeSpd also reduced lactate dehydrogenase activity in the culture supernatant, a parameter of cell death and cell lysis. N(1)-MeSpd diminished intracellular reactive oxygen species production in cultured keratinocytes, and reduced tumor necrosis factor-α, interleukin (IL)-1β and IL-6 gene and protein expression after lipopolysaccharide stimulation. This suggests that some effects of N(1)-MeSpd may be mediated by anti-oxidative and anti-inflammatory effects. These additional properties of N(1)-MeSpd could be clinically important for the treatment of inflammatory alopecias and inflammatory scalp diseases.

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Endocannabinoids limit excessive mast cell maturation and activation in human skin

Cited by 120 publications

References 64 publications

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012

N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

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