scholarly journals Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model

2016 ◽  
Vol 28 (1) ◽  
pp. 22 ◽  
Author(s):  
Gaewon Nam ◽  
Se Kyoo Jeong ◽  
Bu Man Park ◽  
Sin Hee Lee ◽  
Hyun Jong Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cell ◽  
Cell Activation ◽  
Cannabinoid Receptor ◽  
Mast Cell Activation ◽  
Cannabinoid Receptor 1

scholarly journals Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Seok Yong Kang ◽  
Hyo Won Jung ◽  
Joo Hyun Nam ◽  
Woo Kyung Kim ◽  
Jong-Seong Kang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cell ◽  
Calcium Channels ◽  
Cell Activation ◽  
Inflammatory Cells ◽  
Skin Inflammation ◽  
Mast Cell Activation ◽  
Tribulus Terrestris ◽  
Symptom Scores ◽  
Safe Approach

Ethnopharmacological Relevance. In this study, we investigated the effects of Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone-induced atopic dermatitis in mice. Materials and Methods. TF extract was prepared with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was applied to the back skin daily for 24 days. Results. 1% TF extract with 0.1% HC improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract decreased β-hexosaminidase release in RBL-2H3 cells. Conclusions. The present study demonstrates that the topical application of TF extract improves skin inflammation in AD mice, and the mechanism for this effect appears to be related to the modulation of calcium channels and mast cell activation. This outcome suggests that the combination of TF and steroids could be a more effective and safe approach for AD treatment.

scholarly journals Lack of Endogenous Annexin A1 Increases Mast Cell Activation and Exacerbates Experimental Atopic Dermatitis

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 51 ◽  
Author(s):  
Jéssica Parisi ◽  
Mab Corrêa ◽  
Cristiane Gil
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cell ◽  
Cell Activation ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Mast Cell Activation ◽  
Skin Thickness ◽  
Annexin A1 ◽  
Inflammatory Skin Diseases

Annexin A1 (AnxA1) is a protein with potent anti-inflammatory actions and an interesting target that has been poorly explored in skin inflammation. This work evaluated the lack of endogenous AnxA1 in the progression of ovalbumin (OVA)-induced atopic dermatitis (AD)-like skin lesions. OVA/Alum-immunized C57BL/6 male wild-type (WT) and AnxA1 null (AnxA1-/-) mice were challenged with drops containing OVA on days 11, 14–18 and 21–24. The AnxA1-/- AD group exhibited skin with intense erythema, erosion and dryness associated with increased skin thickness compared to the AD WT group. The lack of endogenous AnxA1 also increased IgE relative to WT animals, demonstrating exacerbation of the allergic response. Histological analysis revealed intense eosinophilia and mast-cell activation in AD animals, especially in AnxA1-/-. Both AD groups increased skin interleukin (IL)-13 levels, while IL-17A was upregulated in AnxA1-/- lymph nodes and mast cells. High levels of phosphorylated ERK were detected in keratinocytes from AD groups. However, phospho-ERK levels were higher in the AnxA1-/- when compared to the respective control groups. Our results suggest AnxA1 as an important therapeutic target for inflammatory skin diseases.

Μελέτη της αλληλεπίδρασης νευροπεπτιδίων και κυτταροκινών στην ατοπική δερματίτιδα και ο ρόλος τους στην ενεργοποίηση των μαστοκυττάρων

2013 ◽  
Author(s):  
Κωνσταντίνος-Διονύσιος Αλυσανδράτος
Keyword(s):  
Gene Expression ◽  
Atopic Dermatitis ◽  
Mast Cell ◽  
Mast Cells ◽  
Intracellular Calcium ◽  
Skin Disease ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Lesional Skin ◽  
Mitochondrial Translocation

Atopic dermatitis is a chronic, highly pruritic skin disease, whose prevalence hasincreased considerably in industrialized countries. It is characterized by allergicinflammation in the skin, and has a strong association with other atopic disorders, suchas asthma and allergic rhinitis. The pathogenesis of atopic dermatitis is poorlyunderstood. Stress is thought to worsen skin diseases like atopic dermatitis. Mast cellsare increased in the skin of atopic dermatitis patients, accompanied by an increasednumber of mast cell-nerve interactions. Mast cells also secrete and are activated byneuropeptides and cytokines. The aim of this study was to investigate the interplaybetween neuropeptides and cytokines in the pathogenesis of atopic dermatitis and theirrole on mast cell activation. We speculate that mast cell activation, especially underconditions of stress, accentuates inflammation and angiogenesis, leading to worseningof atopic dermatitis lesions. The primary aim of this doctorate thesis was to investigate the involvement ofneuropeptides and cytokines in atopic dermatitis. For this purpose we used molecularmethods, including ELISA, Luminex and PCR to measure levels of neuropeptides andcytokines that are released by and/or activate mast cells in the serum and lesional skinof atopic dermatitis patients and controls. Our results indicate that the cytokine thymicstromal lymphopoietin (TSLP), is increased in the serum and lesional skin of atopicdermatitis patients, leading to activation of the Th2 response and aggravation of localinflammation. We also found that the neuropeptide neurotensin (NT) is increased in theserum of atopic dermatitis patients, while NT and NT receptor (NTR) gene expression isincreased in the lesional skin compared to controls. The related neuropeptide substanceP (SP) was also found to be increased in the lesional atopic dermatitis skin. NT and SPwere shown to induce corticotropin releasing hormone receptor 1 (CRHR1) expressionand lead to vascular endothelial growth factor (VEGF) release from a human mast cellline, indicating their role in mast cell activation. Gene expression of VEGF, the main proangiogenicfactor, was found to be increased in lesional atopic dermatitis skin, whichhas been previously shown to correlate with progression of local inflammation. Thesefindings may explain why a skin disease like atopic dermatitis is worsened by stress. The molecular mechanism of mast cell activation and degranulation by neuropeptideshas not been studied, but is known to require intracellular calcium and energy. Mitochondria are the primary energy-generating organelles in eukaryotic cells and alsoregulate intracellular calcium. Therefore, we investigated the role of mitochondrialdynamics in mast cell activation and atopic dermatitis. Human umbilical cord bloodderivedmast cells (hCBMCs) and LAD2 mast cells were examined by confocalmicroscopy during activation with IgE/antigen and SP. Degranulation and tumornecrosis factor (TNF) release observed 30 minutes later were accompanied bymitochondrial translocation from a perinuclear location to exocytosis sites. Extracellularcalcium depletion prevented these effects indicating calcium requirement. Mitochondrialdynamics are dependent on the fission dynamin-related protein-1 (DRP1) and itsactivator calcineurin, as inhibition of DRP1 by means of the DRP1 inhibitor MDIVI-1 andsiRNA techniques blocked mitochondrial translocation. Mitochondrial translocation wasalso evident by transmission electron microscopy in skin mast cells from atopicdermatitis biopsies, in which gene expression of calcineurin, DRP1 and SP are highercompared to normal skin. In conclusion, human mast cell activation participates in the pathogenesis of atopicdermatitis and requires mitochondrial dynamics. Atopic dermatitis patients could benefitfrom the development of new therapeutic agents targeting mast cell activation.

scholarly journals Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells

2005 ◽  
Vol 388 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Andrea L. SMALL-HOWARD ◽  
Lori M. N. SHIMODA ◽  
Chaker N. ADRA ◽  
Helen TURNER
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Mast Cell Activation ◽  
Cb1 Cannabinoid Receptor ◽  
Anti Inflammatory ◽  
Camp Levels ◽  
Camp Elevation

Cannabinoids are broadly immunosuppressive, and anti-inflammatory properties have been reported for certain marijuana constituents and endogenously produced cannabinoids. The CB2 cannabinoid receptor is an established constituent of immune system cells, and we have recently established that the CB1 cannabinoid receptor is expressed in mast cells. In the present study, we sought to define a role for CB1 in mast cells and to identify the signalling pathways that may mediate the suppressive effects of CB1 ligation on mast cell activation. Our results show that CB1 and CB2 mediate diametrically opposed effects on cAMP levels in mast cells. The observed long-term stimulation of cAMP levels by the Gαi/o-coupled CB1 is paradoxical, and our results indicate that it may be attributed to CB1-mediated transcriptional regulation of specific adenylate cyclase isoenzymes that exhibit superactivatable kinetics. Taken together, these results reveal the complexity in signalling of natively co-expressed cannabinoid receptors and suggest that some anti-inflammatory effects of CB1 ligands may be attributable to sustained cAMP elevation that, in turn, causes suppression of mast cell degranulation.

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