Testosterone exerts selective anti-inflammatory effects on human skin mast cells in a cell subset dependent manner

Clinically relevant exocytosis of mast cell (MC) mediators can be triggered by high-affinity IgE receptor (FcεRI)-aggregation (allergic route) or by the so-called pseudo-allergic pathway elicited via MAS-related G protein-coupled receptor-X2 (MRGPRX2). The latter is activated by drugs and endogenous neuropeptides. We recently reported that FcεRI-triggered degranulation is attenuated when human skin mast cells are chronically exposed to IL-33. Here, we were interested in the regulation of the MRGPRX2-route. Chronic exposure of skin MCs to IL-33 basically eliminated the pseudo-allergic/neurogenic route as a result of massive MRGPRX2 reduction. This downregulation seemed to partially require c-Jun N-terminal Kinase (JNK), but not p38, the two kinases activated by IL-33 in skin MCs. Surprisingly, however, JNK had a positive effect on MRGPRX2 expression in the absence of IL-33. This was evidenced by Accell®-mediated JNK knockdown and JNK inhibition. In stark contrast to the dampening effect upon prolonged exposure, IL-33 was able to prime for increased degranulation by MRGPRX2 ligands when administered directly before stimulation. This supportive effect depended on p38, but not on JNK activity. Our data reinforce the concept that exposure length dictates whether IL-33 will enhance or attenuate secretion. IL-33 is, thus, the first factor to acutely enhance MRGPRX2-triggered degranulation. Finally, we reveal that p38, rarely associated with MC degranulation, can positively affect exocytosis in a context-dependent manner.

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Trigonelline, An Alkaloid From Leonurus japonicus Houtt., Suppresses Mast Cell Activation and OVA-Induced Allergic Asthma

Frontiers in Pharmacology ◽

10.3389/fphar.2021.687970 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenhui Zhang ◽

Yingling Zhang ◽

Simin Chen ◽

Hong Zhang ◽

Man Yuan ◽

...

Keyword(s):

Mast Cells ◽

Cell Activation ◽

Immunoglobulin E ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Mast Cell Activation ◽

Dependent Manner ◽

Anti Inflammatory

Trigonelline, one of the active compounds from Leonurus japonicus Houtt., has been proven to have pharmacological value in diabetes, the central nervous system and cardiovascular diseases. Recent studies have shown that it may also be beneficial in controlling inflammation. However, the mechanism of the antiallergic effects of trigonelline has not been well studied. As the key effector cells participating in the development of allergies, mast cells have been linked to the pathogenesis of asthma for ages. In this study, we demonstrated the inhibitory effect of trigonelline on activated bone marrow-derived mast cells (BMMCs) and verified its anti-inflammatory properties using an ovalbumin (OVA)-induced asthma model. Trigonelline suppressed BMMC degranulation and decreased the production of the cytokines, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in a dose-dependent manner. The potent mechanism is mainly through the suppression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Trigonelline can alleviate pathological damage in lung tissue and reduce the levels of serum immunoglobulin E (IgE) and T helper 2 (Th2) cytokines. RNA-seq results revealed the HIF-1α to be a potential target for the allergic reaction. Taken together, our study demonstrated that trigonelline can inhibit allergic inflammation in vitro and in vivo, which may provide a basis for novel anti-inflammatory drug development.

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Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3

International Journal of Molecular Sciences ◽

10.3390/ijms22147640 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7640

Author(s):

Sabrina Bilotta ◽

Lakshmi Bhargavi Paruchuru ◽

Katharina Feilhauer ◽

Jörg Köninger ◽

Axel Lorentz

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Activation ◽

Inflammatory Diseases ◽

Critical Role ◽

Mast Cell Activation ◽

Dependent Manner ◽

Cytokines And Chemokines ◽

Mitochondrial Fractions ◽

Anti Inflammatory

Mast cells play a critical role as main effector cells in allergic and other inflammatory diseases. Usage of anti-inflammatory nutraceuticals could be of interest for affected patients. Resveratrol, a natural polyphenol found in red grapes, is known for its positive properties. Here, we analyzed the effects of resveratrol on FcεRI-mediated activation of mature human mast cells isolated from intestinal tissue (hiMC). Resveratrol inhibited degranulation and expression of cytokines and chemokines such as CXCL8, CCL2, CCL3, CCL4, and TNF-α in a dose-dependent manner. Further, resveratrol inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3. ERK1/2 is known to be involved in cytokine expression of hiMC and to directly interact with STAT3. Mitochondrial STAT3 is phosphorylated by ERK1/2 and contributes to mast cell degranulation. We were able to isolate mitochondrial fractions from small hiMC numbers and could show that activation of mitochondrial STAT3 and ERK1/2 in hiMC was also inhibited by resveratrol. Our results indicate that resveratrol inhibits hiMC activation by inhibiting the phosphorylation of mitochondrial and nuclear ERK1/2 and STAT3, and it could be considered as an anti-inflammatory nutraceutical in the treatment of mast cell-associated diseases.

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Anti-Inflammatory Effect of Cyclosporin A on Human Skin Mast Cells

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12499960 ◽

1992 ◽

Vol 98 (5) ◽

pp. 800-804 ◽

Cited By ~ 98

Author(s):

Cristiana Stellato ◽

Amato de Paulis ◽

Anna Ciccarelli ◽

Raffaele Cirillo ◽

Vincenzo Patella ◽

...

Keyword(s):

Mast Cells ◽

Cyclosporin A ◽

Human Skin ◽

Anti Inflammatory ◽

Inflammatory Effect

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Abstract 190: Mesenchymal Stromal Cells (MSCs) Regulate Neutrophil Extracellular Traps (NETs) Through Adenosine

Circulation Research ◽

10.1161/res.121.suppl_1.190 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Rebecca Levit ◽

Eric Shin ◽

LanFang Wang ◽

Kai Xu

Keyword(s):

Fold Increase ◽

Innate Immune ◽

Dependent Manner ◽

Extracellular Traps ◽

Sytox Green ◽

Healthy Donors ◽

A Cell ◽

Anti Inflammatory ◽

Dose Dependent

Background: NETs released by neutrophils may be an important component of inflammation in MI/R. NETs consist of extruded DNA, histone, and other chromatin components and are pro-thrombotic and pro-inflammatory. MSCs as a cell therapy for MI/R may act by modulating the innate immune response including NETs. MSCs convert pro-inflammatory ATP into anti-inflammatory adenosine (ADO) via CD 73, a 5’ ectonucleotidase. Objective: To investigate the role of MSCs in regulating NETs through ADO production. Methods: Neutrophils were freshly isolated from peripheral blood of healthy donors. Human bone marrow derived MSCs were grown under standard conditions. Neutrophils were stimulated to produce NETs by PMA (1 μg/ml) and quantified by Sytox green fluorescence. Some neutrophils were also treated with MSCs or ADO. Results: Neutrophils treated with PMA had a 1.9±0.19, (p<0.05) fold increase in NET formation as quantified by Sytox green florescence. Treatment with MSCs in 1:10 ratio prevented increased NET production in response to PMA (1.02±0.12 fold increase). Pretreatment of MSCs with a CD 73 inhibitor APCP reduced their ability to prevent NET formation in some donors (1.62±0.10). ADO decreased NET formation in a dose dependent manner. Conclusion: MSCs may inhibit NET formation through ADO signaling and could be an important mechanism of MSC anti-inflammatory effects in MI/R. Future studies will investigate the ability of MSCs to inhibit NET formation in MI/R.

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Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia

Scientific Reports ◽

10.1038/s41598-017-15022-3 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 17

Author(s):

Takuya Kotani ◽

Ryota Masutani ◽

Takayasu Suzuka ◽

Katsuhiro Oda ◽

Shigeki Makino ◽

...

Keyword(s):

T Cells ◽

Lung Injury ◽

Mouse Model ◽

Interstitial Pneumonia ◽

Cell Number ◽

Dependent Manner ◽

Activated Macrophages ◽

A Cell ◽

Anti Inflammatory ◽

Differentiation And Proliferation

Abstract Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner. AdSCs inhibited the production of pro-inflammatory cytokines such as TNF-α and IL-12 in activated macrophages, and AdSCs also induced the apoptosis of activated macrophages. AdSCs inhibited the differentiation and proliferation of Th2-type mCD4+ T cells but promoted the differentiation and proliferation of regulatory T cells, suggesting that the phenotypic conversion of T cells may be one of the mechanisms for the anti-inflammatory effect of AdSCs on pulmonary fibrosis. These findings suggest that intravenous AdSCs could be a promising treatment for patients with interstitial pneumonia.

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Anti-Inflammatory Effect of FK-506 on Human Skin Mast Cells

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12614216 ◽

1992 ◽

Vol 99 (6) ◽

pp. 723-728 ◽

Cited By ~ 98

Author(s):

Amato. de Paulis ◽

Cristiana Stellato ◽

Raffaele Cirillo ◽

Anna Ciccarelli ◽

Alfonso Oriente ◽

...

Keyword(s):

Mast Cells ◽

Human Skin ◽

Fk 506 ◽

Anti Inflammatory ◽

Inflammatory Effect

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Spindle scaling mechanisms

Essays in Biochemistry ◽

10.1042/ebc20190064 ◽

2020 ◽

Vol 64 (2) ◽

pp. 383-396

Author(s):

Lara K. Krüger ◽

Phong T. Tran

Keyword(s):

Cell Size ◽

Spindle Assembly ◽

Dependent Manner ◽

Post Translational Modification ◽

Size Dependent ◽

A Cell ◽

Chromosome Separation ◽

Spindle Elongation ◽

Protein Gradients ◽

Spindle Structure

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

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Antioxidant and Anti-inflammatory Activities of Organic and Aqueous Extracts of Northeast Algerian Marrubium vulgare

Phytothérapie ◽

10.3166/phyto-2018-0106 ◽

2018 ◽

Vol 16 (S1) ◽

pp. S119-S129

Author(s):

I. Namoune ◽

B. Khettal ◽

A.M. Assaf ◽

S. Elhayek ◽

L. Arrar

Keyword(s):

Ethyl Acetate ◽

Methanolic Extract ◽

Ethyl Acetate Extract ◽

Interleukin 1 ◽

Total Phenolic ◽

Dependent Manner ◽

Aqueous Extracts ◽

Traditional Use ◽

Marrubium Vulgare ◽

Anti Inflammatory

Marrubium vulgare (Lamiaceae) is frequently used in traditional medicine to treat many illnesses from ancient times. Its beneficial effects include antibacterial, antioedematogenic, and analgesic activities. This study was designed to evaluate the antioxidant and anti-inflammatory activities of organic and aqueous extracts of the leaves, the flowers, the stems, and the roots of Marrubium vulgare. The total phenolic and flavonoid contents as well as the antioxidant and the anti-inflammatory effects of methanol, chloroform, ethyl acetate, and aqueous extracts have been investigated by using different in-vitro methods. It was found that the ethyl acetate extract from Marrubium vulgare stems had the highest total phenolic content, while the ethyl acetate extract from the leaves yielded a high concentration of flavonoids. The ethyl acetate extract from the stems exhibited the highest activity in scavenging of 2,2-diphenyl- 1-picrylhydrazyl (DPPH), as well as in protecting erythrocytes. The leaves aqueous extract exhibited the highest ferrous chelating activity and its methanolic extract was found to be the strongest inhibitor of lipid peroxidation in β-carotene bleaching assay. The leaves chloroform extracts as well as the flowers methanol, chloroform, and ethyl acetate extracts were found to decrease the pro-inflammatory tumor necrosis factor alpha (TNF-α) cytokine levels in a dose-dependent manner. On the other hand, the flowers methanolic extract and the leaves methanol, ethyl acetate, and aqueous extracts decreased the interleukin-1 beta (IL- 1β) release. It was also found that the methanol extract from the flowers and the chloroform extract from the stems of Marrubium vulgare inhibited interleukin-8 (IL-8) release. This study provides a scientific basis for the traditional use of Marrubium vulgare as an anti-inflammatory agent and for the plant to be considered as an important resource of natural antioxidants.

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High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽

10.3390/nu11091981 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1981 ◽

Cited By ~ 9

Author(s):

Qiufen Mo ◽

Aikun Fu ◽

Lingli Deng ◽

Minjie Zhao ◽

Yang Li ◽

...

Keyword(s):

Lipid Metabolism ◽

Systemic Inflammation ◽

Body Weight Gain ◽

High Dose ◽

Dependent Manner ◽

Glucose And Lipid Metabolism ◽

Glycerol Monolaurate ◽

Indigenous Microbiota ◽

Anti Inflammatory ◽

Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

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