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Mast cell asthma

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https://www.readbyqxmd.com/read/29763661/prominent-release-of-lipoxygenase-generated-mediators-in-a-murine-house-dust-mite-induced-asthma-model
#1
Johan Kolmert, Sergio Piñeiro-Hermida, Craig E Wheelock, Mats Hamberg, Joshua A Gregory, Icíar P López, Alexander Fauland, Sven-Erik Dahlén, José G Pichel, Mikael Adner
The profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of ω3-, ω6- and ω9-derived polyunsaturated fatty acids in bronchoalveolar lavage fluid (BALF) after 4-weeks of repeated house dust mite (HDM) exposure in a murine (C57BL/6) asthma model. The challenge induced airway hyperresponsiveness, pulmonary eosinophil infiltration, but with low and unchanged mast cell numbers. Of the 112 screened LMs, 26 were increased between 2 to >25-fold in BALF with HDM treatment (p < 0...
May 12, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29759032/tim-3-expressing-mast-cells-are-present-in-chronic-rhinosinusitis-with-nasal-polyps
#2
Erica Corredera, Binh L Phong, John A Moore, Lawrence P Kane, Stella E Lee
Objectives To identify whether TIM-3 expression is present in the mast cell population within nasal polyps and to determine its correlation with clinical severity in patients with chronic rhinosinusitis with nasal polyposis. Study Design Basic science, translational study. Setting Nasal polyp tissue collected from patients seen at a tertiary care hospital (2015-2016). Subjects and Methods Nasal polyp tissue obtained during functional endoscopic sinus surgery (n = 24) was enzymatically digested into epithelial and stromal fractions...
May 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29755466/controlling-mast-cell-activation-and-homeostasis-work-influenced-by-bill-paul-that-continues-today
#3
REVIEW
Heather L Caslin, Kasalina N Kiwanuka, Tamara T Haque, Marcela T Taruselli, H Patrick MacKnight, Anuya Paranjape, John J Ryan
Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29748238/mir-302e-attenuates-allergic-inflammation-in-vitro-model-by-targeting-rela
#4
Lifeng Xiao, Li Jiang, Qi Hu, Yuru Li
Allergic inflammation is the foundation of allergic rhinitis and asthma. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in allergic diseases is limited. Herein, we reported that microRNA-302e (miR-302e) serves as an important regulator of allergic inflammation in human mast cell line, HMC-1 cells. Our results showed that miR-302e is the dominant member of miR-302 family expressed in HMC-1 cells. Moreover, the expression of miR-302e was significantly decreased in response to phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 or ovalbumin (OVA) stimulation...
May 10, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29707474/vitamin-a-and-d-in-allergy-from-experimental-animal-models-and-cellular-studies-to-human-disease
#5
REVIEW
Karin Hufnagl, Erika Jensen-Jarolim
Introduction: Vitamins A and D are able to modulate innate and adaptive immune responses and may therefore influence the development and the course of allergic diseases. Materials and methods: This article reviews the current evidence for the experimental effects of vitamins A and D in vivo in animal models and on immune cells in vitro , and discusses their translational implication. A systematic literature search over the last 10 years was performed using MEDLINE and PubMed databases...
2018: Allergo Journal International
https://www.readbyqxmd.com/read/29685001/cysteinyl-leukotrienes-c4-and-d4-downregulate-human-mast-cell-expression-of-toll-like-receptors-1-through-7
#6
V Karpov, R Ilarraza, A Catalli, M Kulka
Cysteinyl leukotrienes (CysLT) are potent inflammatory lipid molecules that mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability. As a result, CysLT receptor antagonists (LRA), such as montelukast, have been used to effectively treat patients with asthma. We have recently shown that mast cells are necessary modulators of innate immune responses to bacterial infection and an important component of this innate immune response may involve the production of CysLT...
March 2018: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/29683527/modulation-of-allergic-responses-by-mitochondrial-stat3-inhibitors
#7
Tal Erlich, Israa Sharkia, Nadine Landolina, Miri Assayag, Omer Goldberger, Neville Berkman, Francesca Levi-Schafer, Ehud Razin
Recently we have shown that mast cell mitochondrial STAT3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically-mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT3 inhibitors (Mitocur-1 and Mitocur-3) modulate the allergic response. Here we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT3 inhibitors had no effect on STAT3 target gene expression...
April 23, 2018: Allergy
https://www.readbyqxmd.com/read/29678746/thirdhand-smoke-component-can-exacerbate-a-mouse-asthma-model-via-mast-cells
#8
Mang Yu, Kaori Mukai, Mindy Tsai, Stephen J Galli
BACKGROUND: Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for developing asthma and for exacerbation of that disease if they already have it, how exposure to THS may influence the development or exacerbation of asthma remains unknown. OBJECTIVE: We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a model elicited in mice by repeated intranasal challenge with cockroach antigen (CRA)...
April 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29677491/the-allergen-der-p3-from-house-dust-mite-stimulates-store-operated-ca-2-channels-and-mast-cell-migration-through-par4-receptors
#9
Yu-Ping Lin, Charmaine Nelson, Holger Kramer, Anant B Parekh
The house dust mite is the principal source of perennial aeroallergens in man. How these allergens activate innate and adaptive immunity is unclear, and therefore, there are no therapies targeting mite allergens. Here, we show that house dust mite extract activates store-operated Ca2+ channels, a common signaling module in numerous cell types in the lung. Activation of channel pore-forming Orai1 subunits by mite extract requires gating by STIM1 proteins. Although mite extract stimulates both protease-activated receptor type 2 (PAR2) and PAR4 receptors, Ca2+ influx is more tightly coupled to the PAR4 pathway...
April 19, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29668121/lipofection-of-plasmid-dna-into-human-mast-cell-lines-using-lipid-nanoparticles-generated-by-microfluidic-mixing
#10
Brett A Duguay, Kate Wei-Chen Huang, Marianna Kulka
Mast cells are important immune cells that have significant roles in mediating allergy and asthma. Therefore, studying the molecular mechanisms regulating these and other processes in mast cells is important to elucidate. Methods such as lipofection, transduction, and electroporation are often employed to dissect these mechanisms by disrupting gene expression in mast cell lines. However, as with other leukocytes, human mast cells (HMCs) are often refractory to the delivery of plasmids by lipofection. In this study, we investigated the utility of lipid nanoparticles (LNPs) containing the ionizable cationic lipids 1,2-dioleoyloxy-3-dimethylaminopropane, 1,2-dioleyloxy-3-dimethylaminopropane, or 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane for the delivery of plasmid DNA into HMC lines...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29665659/suppressive-effect-of-4-hydroxy-2-4-hydroxyphenethyl-isoindoline-1-3-dione-on-ovalbumin-induced-allergic-asthma
#11
Jin Huang, Mingzhi Su, Bo-Kyung Lee, Mee-Jeong Kim, Jee H Jung, Dong-Soon Im
4-Hydroxy-2-(4-hydroxyphenethyl)isoindoline-1,3-dione (PD1) is a synthetic phthalimide derivative of a marine compound. PD1 has peroxisome proliferator-activated receptor (PPAR) γ agonistic and anti-inflammatory effects. This study aimed to investigate the effect of PD1 on allergic asthma using rat basophilic leukemia (RBL)-2H3 mast cells and an ovalbumin (OVA)-induced asthma mouse model. In vitro , PD1 suppressed β-hexosaminidase activity in RBL-2H3 cells. In the OVA-induced allergic asthma mouse model, increased inflammatory cells and elevated Th2 and Th1 cytokine levels were observed in bronchoalveolar lavage fluid (BALF) and lung tissue...
April 18, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29661938/dual-functionality-of-%C3%AE-tryptase-protomers-as-both-proteases-and-cofactors-in-the-active-tetramer
#12
Henry R Maun, Peter S Liu, Yvonne Franke, Charles Eigenbrot, William F Forrest, Lawrence B Schwartz, Robert A Lazarus
Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of the allergic inflammatory responses in asthma. During acute hypersensitivity reactions, mast cells degranulate, releasing active tetramer as a complex with proteoglycans. Extensive efforts have focused on developing therapeutic β-tryptase inhibitors, but its unique activation mechanism is less well explored. Tryptase is active only after proteolytic removal of the pro-domain followed by tetramer formation via two distinct symmetry-related interfaces...
April 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29644714/design-synthesis-and-biological-evaluation-of-2-substituted-2-3-4-9-tetrahydrospiro-%C3%AE-carboline-3-carboxylic-acid-derivatives-as-first-in-class-mast-cell-stabilizers
#13
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh, Amteshwar S Jaggi, Nirmal Singh
Mast cell degranulation plays a momentous role in myriad diseases like asthma, eczema, allergic rhinitis, and conjunctivitis as well as anaphylactic shock; hence, there is an unmet need for developing new mast cells stabilizers. The reported mast cell stabilizers have a heterocyclic moiety and an acidic group. Furthermore, the role of tryptophan in suppression of mast cell activation is established. Hence, we prepared constrained analogs of tryptophan, which are derivatives of 2,3,4,9-tetrahydrospiro-β-carboline-3-carboxylic acid, and evaluated them for ex vivo inhibition of compound 48/80-induced mast degranulation activity...
April 12, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29599294/munc18-2-but-not-munc18-1-or-munc18-3-controls-compound-and-single-vesicle-regulated-exocytosis-in-mast-cells
#14
Berenice A Gutierrez, Miguel A Chavez, Alejandro I Rodarte, Marco Ramos, Andrea Dominguez, Youlia Petrova, Alfredo J Davalos, Renan M Costa, Ramon Elizondo, Michael J Tuvim, Burton F Dickey, Alan R Burns, Ruth Heidelberger, Roberto Adachi
Mast cells (MCs) play pivotal roles in many inflammatory conditions including infections, anaphylaxis and asthma. MCs store immunoregulatory compounds in their large cytoplasmic granules and, upon stimulation, secrete them via regulated exocytosis. Exocytosis in many cells requires the participation of Munc18 proteins (also known as syntaxin-binding proteins), and we found that mature MCs express all three mammalian isoforms: Munc18 1, 2 and 3. To study their functions in MC effector responses and test the role of MC degranulation in anaphylaxis, we used conditional knockout (cKO) mice in which each Munc18 protein was deleted exclusively in MCs...
March 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29572542/aryl-hydrocarbon-receptor-signaling-promotes-ormdl3-dependent-generation-of-sphingosine-1-phosphate-by-inhibiting-sphingosine-1-phosphate-lyase
#15
Hsueh-Chun Wang, Tzu-Hsuan Wong, Li-Ting Wang, Hsiang-Han Su, Hsiu-Yueh Yu, Ai-Hsuan Wu, Yu-Chun Lin, Hua-Ling Chen, Jau-Ling Suen, Shih-Hsien Hsu, Li-Chen Chen, Yufeng Zhou, Shau-Ku Huang
Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of sphingolipid metabolism, is believed to have a role in immunity and inflammation, but their potential crosstalk is currently unknown. We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism. We showed that AhR ligands, including an environmental polycyclic aromatic hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL) activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge...
March 23, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29569388/antigen-specific-airway-il-33-production-depends-on-fc%C3%AE-r-mediated-incorporation-of-the-antigen-by-alveolar-macrophages-in-sensitized-mice
#16
Takeshi Nabe, Masaya Matsuda, Tomoki Ishida, Nau Tsujimoto, Hitomi Kido, Haruna Kanaya, Hiromu Takahashi, Naoki Takemoto, Miku Nomura, Keiichi Ishihara, Satoshi Akiba, Nobuaki Mizutani
Although interleukin (IL)-33 is a candidate for the aggravation of asthma, the mechanisms underlying antigen-specific IL-33 production in the lung are unclear. Therefore, we analyzed the mechanisms in mice. Intratracheal administration of ovalbumin (OVA) evoked increases in IL-33 and IL-33 mRNA in the lungs of both non-sensitized and OVA-sensitized mice, and the increases in the sensitized mice were significantly higher than in the non-sensitized mice. However, intratracheal administration of bovine serum albumin (BSA) did not increase the IL-33 level in the OVA-sensitized mice...
March 22, 2018: Immunology
https://www.readbyqxmd.com/read/29552874/allergic-conjunctivitis-current-concepts-on-pathogenesis-and-management
#17
M Sacchetti, I Abicca, A Bruscolini, C Cavaliere, M Nebbioso, A Lambiase
Allergic conjunctivitis (AC) includes a wide spectrum of clinical entities characterized by different incidence, age of onset, natural course, clinical outcome and response to treatment. Taken together, they represent one of the most frequent ocular surface diseases affecting more than 30&#x0025; of the young-adult population and show an increasing incidence over the years. Moreover, comorbidities with other systemic atopic conditions such as asthma, atopic dermatitis and rhinitis require a multidisciplinary approach...
January 2018: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/29540770/il-33-st2-signalling-and-crosstalk-with-fc%C3%AE%C2%B5ri-and-tlr4-is-targeted-by-the-parasitic-worm-product-es-62
#18
Dimity H Ball, Lamyaa Al-Riyami, William Harnett, Margaret M Harnett
ES-62 is a secreted parasitic worm-derived immunomodulator that exhibits therapeutic potential in allergy by downregulating aberrant MyD88 signalling to normalise the inflammatory phenotype and mast cell responses. IL-33 plays an important role in driving mast cell responses and promoting type-2 allergic inflammation, particularly with respect to asthma, via MyD88-integrated crosstalk amongst the IL-33 receptor (ST2), TLR4 and FcεRI. We have now investigated whether ES-62 targets this pathogenic network by subverting ST2-signalling, specifically by characterising how the functional outcomes of crosstalk amongst ST2, TLR4 and FcεRI are modulated by the worm product in wild type and ST2-deficient mast cells...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29534664/the-role-of-interleukin-33-in-pathogenesis-of-bronchial-asthma-new-experimental-data
#19
REVIEW
M R Khaitov, A R Gaisina, I P Shilovskiy, V V Smirnov, G V Ramenskaia, A A Nikonova, R M Khaitov
Interleukin-33 (IL-33) belongs to the IL-1 cytokine family and plays an important role in modulating immune system by inducing Th2 immune response via the ST2 membrane receptor. Epithelial cells are the major producers of IL-33. However, IL-33 is also secreted by other cells, e.g., bone marrow cells, dendritic cells, macrophages, and mast cells. IL-33 targets a broad range of cell types bearing the ST2 surface receptor. Many ST2-positive cells, such as Th2 cells, mast cells, basophils, and eosinophils, are involved in the development of allergic bronchial asthma (BA)...
January 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29532264/propofol-attenuates-airway-inflammation-in-a-mast-cell-dependent-mouse-model-of-allergic-asthma-by-inhibiting-the-toll-like-receptor-4-reactive-oxygen-species-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway
#20
Hong-Yi Li, Jing-Xia Meng, Zhen Liu, Xiao-Wen Liu, Yu-Guang Huang, Jing Zhao
Propofol, an intravenous anesthetic agent widely used in clinical practice, is the preferred anesthetic for asthmatic patients. This study was designed to determine the protective effect and underlying mechanisms of propofol on airway inflammation in a mast cell-dependent mouse model of allergic asthma. Mice were sensitized by ovalbumin (OVA) without alum and challenged with OVA three times. Propofol was given intraperitoneally 0.5 h prior to OVA challenge. The inflammatory cell count and production of cytokines in the bronchoalveolar lavage fluid (BALF) were detected...
March 12, 2018: Inflammation
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