Phenethyl isothiocyanate decreases thymic stromal lymphopoietin-induced inflammatory reactions in mast cells

2017 ◽  
Vol 42 (1) ◽  
pp. e12449
Author(s):  
Na-Ra Han ◽  
Phil-Dong Moon ◽  
Ka-Jung Ryu ◽  
Hyung-Min Kim ◽  
Hyun-Ja Jeong
Keyword(s):  
Mast Cells ◽  
Thymic Stromal Lymphopoietin ◽  
Phenethyl Isothiocyanate ◽  
Inflammatory Reactions

scholarly journals Thymic Stromal Lymphopoietin Interferes with the Apoptosis of Human Skin Mast Cells by a Dual Strategy Involving STAT5/Mcl-1 and JNK/Bcl-xL

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 829 ◽  
Author(s):  
Tarek Hazzan ◽  
Jürgen Eberle ◽  
Margitta Worm ◽  
Magda Babina
Keyword(s):  
Mast Cells ◽  
Myeloid Cell ◽  
B Cell Lymphoma ◽  
Thymic Stromal Lymphopoietin ◽  
Potential Contribution ◽  
Apoptosis Resistance ◽  
Distinct Component ◽  
Inflammatory Reactions ◽  
Dual Strategy ◽  
High Level

Mast cells (MCs) play critical roles in allergic and inflammatory reactions and contribute to multiple pathologies in the skin, in which they show increased numbers, which frequently correlates with severity. It remains ill-defined how MC accumulation is established by the cutaneous microenvironment, in part because research on human MCs rarely employs MCs matured in the tissue, and extrapolations from other MC subsets have limitations, considering the high level of MC heterogeneity. Thymic stromal lymphopoietin (TSLP)—released by epithelial cells, like keratinocytes, following disturbed homeostasis and inflammation—has attracted much attention, but its impact on skin MCs remains undefined, despite the vast expression of the TSLP receptor by these cells. Using several methods, each detecting a distinct component of the apoptotic process (membrane alterations, DNA degradation, and caspase-3 activity), our study pinpoints TSLP as a novel survival factor of dermal MCs. TSLP confers apoptosis resistance via concomitant activation of the TSLP/ signal transducer and activator of transcription (STAT)-5 / myeloid cell leukemia (Mcl)-1 route and a newly uncovered TSLP/ c-Jun-N-terminal kinase (JNK)/ B-cell lymphoma (Bcl)-xL axis, as evidenced by RNA interference and pharmacological inhibition. Our findings highlight the potential contribution of TSLP to the MC supportive niche of the skin and, vice versa, highlight MCs as crucial responders to TSLP in the context of TSLP-driven disorders.

scholarly journals Thymic Stromal Lymphopoietin Promotes MRGPRX2-Triggered Degranulation of Skin Mast Cells in a STAT5-Dependent Manner with Further Support from JNK

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Magda Babina ◽  
Zhao Wang ◽  
Kristin Franke ◽  
Torsten Zuberbier
Keyword(s):  
Mast Cells ◽  
Priming Effect ◽  
Skin Diseases ◽  
Thymic Stromal Lymphopoietin ◽  
Dependent Manner ◽  
Atopic Diseases ◽  
Time Points ◽  
Histamine Liberation ◽  
Atopic Skin ◽  
Th2 Immunity

Thymic stromal lymphopoietin (TSLP) is released by epithelial cells following disturbed homeostasis to act as “alarmin” and driver of Th2-immunity. Aberrant TSLP expression is a hallmark of atopic diseases, including atopic dermatitis (AD). Mast cells (MCs) are overabundant in AD lesions and show signs of degranulation, but it remains unknown whether TSLP contributes to granule discharge. Degranulation of skin MCs proceeds via two major routes, i.e., FcεRI-dependent (allergic) and MRGPRX2-mediated (pseudo-allergic/neurogenic). Evidence is accumulating that MRGPRX2 may be crucial in the context of skin diseases, including eczema. The current study reveals TSLP as a novel priming factor of human skin MCs. Interestingly, TSLP selectively cooperates with MRGPRX2 to support granule discharge, while it does not impact spontaneous or FcεRI-driven exocytosis. TSLP-assisted histamine liberation triggered by compound 48/80 or Substance P, two canonical MRGPRX2 agonists, was accompanied by an increase in CD107a+ cells (a MC activation marker). The latter process was less potent, however, and detectable only at the later of two time points, suggesting TSLP may prolong opening of the granules. Mechanistically, TSLP elicited phosphorylation of STAT5 and JNK in skin MCs and the reinforced degranulation critically depended on STAT5 activity, while JNK had a contributory role. Results from pharmacological inhibition were confirmed by RNA-interference, whereby silencing of STAT5 completely abolished the priming effect of TSLP on MRGPRX2-mediated degranulation. Collectively, TSLP is the first factor to favor MRGPRX2- over FcεRI-triggered MC activation. The relevance of TSLP, MCs and MRGPRX2 to pruritis and atopic skin pathology indicates broad repercussions of the identified connection.

scholarly journals Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells

2007 ◽  
Vol 204 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Zoulfia Allakhverdi ◽  
Michael R. Comeau ◽  
Heidi K. Jessup ◽  
Bo-Rin Park Yoon ◽  
Avery Brewer ◽  
...  
Keyword(s):  
Mast Cells ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immunoglobulin E ◽  
Interleukin 1 ◽  
Allergic Inflammation ◽  
Thymic Stromal Lymphopoietin ◽  
Microbial Products ◽  
Necrosis Factor

Compelling evidence suggests that the epithelial cell–derived cytokine thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell–mediated T helper (Th)2 response. Here, we describe how TSLP might initiate and aggravate allergic inflammation in the absence of T lymphocytes and immunoglobulin E antibodies via the innate immune system. We show that TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs). We next report that TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines. Direct epithelial cell–mediated, TSLP-dependent activation of MCs may play a central role in “intrinsic” forms of atopic diseases and explain the aggravating role of infection and scratching in these diseases.

scholarly journals Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4314 ◽  
Author(s):  
José Antonio Uranga ◽  
Vicente Martínez ◽  
Raquel Abalo
Keyword(s):  
Mast Cell ◽  
Irritable Bowel Syndrome ◽  
Mast Cells ◽  
Gastrointestinal Disorder ◽  
Inflammatory Reactions ◽  
Food Components ◽  
Daily Food ◽  
Release Histamine ◽  
Irritable Bowel

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.

Anti-allergic inflammatory effect of vanillic acid through regulating thymic stromal lymphopoietin secretion from activated mast cells

2017 ◽  
Vol 32 (24) ◽  
pp. 2945-2949 ◽  
Author(s):  
Hyun-Ja Jeong ◽  
Sun-Young Nam ◽  
Hee-Yun Kim ◽  
Mu Hyun Jin ◽  
Mi Hye Kim ◽  
...  
Keyword(s):  
Mast Cells ◽  
Vanillic Acid ◽  
Thymic Stromal Lymphopoietin ◽  
Inflammatory Effect

scholarly journals Systemic Mastocytosis and Essential Thrombocythemia: Case Report and Literature Overview

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 528
Author(s):  
Mauro Cancian ◽  
Elisabetta Cosi ◽  
Marco Pizzi ◽  
Sandro Giannini ◽  
Irene Bertozzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Systemic Mastocytosis ◽  
Inflammatory Reactions ◽  
Zolendronic Acid ◽  
Literature Overview ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Mastocytosis is a rare disease in which heightened amounts of mast cells accumulate in the skin, bone marrow, and other visceral organs. Upon activation, mast cells release a wide variety of preformed or newly synthesized mediators which can induce allergic symptoms and inflammatory reactions. Mastocytosis is diagnosed by biopsy and can be divided into cutaneous and systemic mastocytosis (SM). The first one affects the skin and is relatively benign, whilst SM, which involves bone marrow and other organs, may be aggressive and associate with both myelodisplastic and myeloproliferative diseases. Here we present a case of SM associated with essential thrombocythemia and complicated by severe osteoporosis, successfully treated with hydroxyurea, low-dose aspirin and zolendronic acid.

Stem Cell Factor and Thymic Stromal Lymphopoietin Overexpression With Correlation to Mast Cells in Superior Limbic Keratoconjunctivitis

Cornea ◽  
2015 ◽  
Vol 34 (11) ◽  
pp. 1487-1492 ◽  
Author(s):  
Yi-Chen Sun ◽  
Hau-Min Liou ◽  
Elizabeth P. Shen ◽  
Fung-Rong Hu
Keyword(s):  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Thymic Stromal Lymphopoietin
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