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Mast Cell Activation

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https://www.readbyqxmd.com/read/28087322/cutaneous-exposure-to-vesicant-phosgene-oxime-acute-effects-on-the-skin-and-systemic-toxicity
#1
Neera Tewari-Singh, Dinesh G Goswami, Rama Kant, Claire R Croutch, Robert P Casillas, David J Orlicky, Rajesh Agarwal
Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model...
January 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28078840/mast-cell-and-cancer-with-special-emphasis-on-il-37-an-anti-inflammatory-and-inhibitor-of-innate-immunity-new-frontiers
#2
F Carinci, G Lessiani, E Spinas, S K Kritas, G Ronconi, Al Caraffa, P Conti
Mast cells (MCs) are mediators of allergy and inflammation and participate in the growth of cancer cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain tumors where they can be recruited by tumor-derived chemoattractants, such as monocyte chemotactic protein-1 (MCP-1), RANTES and stem cell factor (SCF) to selectively secrete inflammatory molecules including chemical mediators and cytokines (TNF, IL-6 and IL-1). However, MC differentiation pathways and heterogeneity in cancer are still poorly understood...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28074060/s100a8-a9-and-s100a9-reduce-acute-lung-injury
#3
Yuka Hiroshima, Kenneth Hsu, Nicodemus Tedla, Sze Wing Wong, Sharron Chow, Naomi Kawaguchi, Carolyn L Geczy
S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic comparison of their effects in vivo are limited. Here we assess inflammation in murine lung following S100A9 and S100A8/A9 inhalation. Unlike S100A8, S100A9 promoted mild neutrophil and lymphocyte influx, possibly mediated in part, by increased mast cell degranulation and selective upregulation of some chemokine genes, particularly CXCL-10...
January 11, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28073916/ceramide-cd300f-binding-inhibits-lipopolysaccharide-induced-skin-inflammation
#4
Emiko Shiba, Kumi Izawa, Ayako Kaitani, Masamichi Isobe, Akie Maehara, Koichiro Uchida, Keiko Maeda, Nobuhiro Nakano, Hideoki Ogawa, Ko Okumura, Toshio Kitamura, Toshiaki Shimizu, Jiro Kitaura
Lipopolysaccharide (LPS) triggers inflammatory responses; however, the negative regulation of LPS responses in vivo remains poorly understood. CD300f is an inhibitory receptor among the CD300 family of paired activating and inhibitory receptors. We have previously identified ceramide as a ligand for CD300f and shown that the binding of ceramide to CD300f inhibits IgE-mediated mast cell activation and allergic responses in mouse models. Here we identify the critical role of CD300f in inhibiting LPS-induced skin inflammation...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28063824/development-of-safe-and-potent-o-w-emulsion-of-paclitaxel-to-treat-peritoneal-dissemination
#5
Ken-Ichi Ogawara, Yoshiko Fukuoka, Yuta Yoshizawa, Toshikiro Kimura, Kazutaka Higaki
To develop a safer and more potent paclitaxel (PTX) formulation, we prepared various O/W emulsions by using egg phosphatidylcholine, Tween 80, and a mixture of triglycerides with different fatty acid chain lengths as the co-surfactant, surfactant, and oil phase component, respectively. The mean particle diameters of the PTX-emulsions prepared were around 100 nm. The PTX-emulsions did not provoke histamine release from rat mast cells and did not show any significant hemolytic activity, suggesting that PTX-emulsions are biocompatible...
January 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28062735/the-ability-of-btk-inhibitors-to-sequester-y551-and-prevent-phosphorylation-determines-potency-for-inhibition-of-fcr-but-not-b-cell-receptor-signaling
#6
Andrew T Bender, Anna Gardberg, Albertina Pereira, Theresa Johenson, Yin Wu, Roland Grenningloh, Jared Head, Federica Morandi, Philipp Haselmayer, Lesley Liu-Bujalski
Bruton's tyrosine kinase (Btk) is expressed in a variety of hematopoietic cells. Btk has been demonstrated to regulate signaling downstream of the B cell receptor (BCR), Fc receptors (FcR), and toll like receptors (TLRs). Btk has become an attractive drug target as Btk inhibition may provide significant efficacy by blocking multiple disease mechanisms simultaneously. Consequently, a large number of Btk inhibitors have been developed. The compounds have diverse binding modes and both reversible and irreversible inhibitors have been developed...
January 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28058543/genomic-profiling-of-canine-mast-cell-tumors-identifies-dna-copy-number-aberrations-associated-with-kit-mutations-and-high-histological-grade
#7
Hiroyuki Mochizuki, Rachael Thomas, Scott Moroff, Matthew Breen
Mast cell tumor (MCT) is the most common skin malignancy of domestic dogs and presents with a widely variable clinical behavior. Although activating KIT mutations are present in approximately 20% of canine MCTs, molecular etiology is largely unknown for the majority of this cancer. Characterization of genomic alterations in canine MCTs may identify genomic regions and/or genes responsible for their development and progression, facilitating the discovery of new therapeutic targets and improved clinical management of this heterogeneous cancer...
January 5, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28057422/structure-activity-relationship-study-and-discovery-of-indazole-3-carboxamides-as-calcium-release-activated-calcium-channel-blockers
#8
Sha Bai, Masazumi Nagai, Steffi K Koerner, Aristidis Veves, Lijun Sun
Aberrant activation of mast cells contributes to the development of numerous diseases including cancer, autoimmune disorders, as well as diabetes and its complications. The influx of extracellular calcium via the highly calcium selective calcium-release activated calcium (CRAC) channel controls mast cell functions. Intracellular calcium homeostasis in mast cells can be maintained via the modulation of the CRAC channel, representing a critical point for therapeutic interventions. We describe the structure-activity relationship study (SAR) of indazole-3-carboxamides as potent CRAC channel blockers and their ability to stabilize mast cells...
December 27, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28054578/reply-the-complexity-of-substance-p-mediated-mast-cell-activation
#9
Guo-Ping Shi, Ilze Bot, Petri T Kovanen
No abstract text is available yet for this article.
January 5, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28053900/the-possible-mode-of-antitussive-and-expectorant-activity-of-the-ethanol-seed-extracts-of-picralima-nitida-stapf-th-h-durand
#10
Gabriel Dapaah, George Asumeng Koffuor, Priscilla Kolibea Mante, Inemesit Okon Ben
It has been established that Picralima nitida has antitussive effect. This study therefore aimed at determining the possible mode of antitussive and expectorant activity of an ethanolic seed extract of P. nitida (PNE). The muco-suppressant, mast cell stabilization, and the anxiolytic effects of PNE were ascertained using ammonium chloride-induced phenol red secretion in BALB/c mice; compound 48/80-induced mesenteric mast cell degranulation assay; and the open field and the elevated plus maze models respectively...
January 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28053237/highly-selective-cleavage-of-cytokines-and-chemokines-by-the-human-mast-cell-chymase-and-neutrophil-cathepsin-g
#11
Zhirong Fu, Michael Thorpe, Rahel Alemayehu, Ananya Roy, Jukka Kervinen, Lawrence de Garavilla, Magnus Åbrink, Lars Hellman
Human mast cell chymase (HC) and human neutrophil cathepsin G (hCG) show relatively similar cleavage specificities: they both have chymotryptic activity but can also cleave efficiently after leucine. Their relatively broad specificity suggests that they may cleave almost any substrate if present in high enough concentrations or for a sufficiently long time. A number of potential substrates have been identified for these enzymes and, recently, these enzymes have also been implicated in regulating cytokine activity by cleaving numerous cytokines and chemokines...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28049206/novel-mechanisms-underlying-the-therapeutic-effect-of-glycomacropeptide-on-allergy-change-in-gut-microbiota-upregulation-of-tgf-%C3%AE-and-inhibition-of-mast-cells
#12
Mariela Jiménez, Daniel Cervantes-García, Yualli Haydee Muñoz, Alejandra García, Luis Miguel Haro, Eva Salinas
BACKGROUND: The prevalence of allergic diseases is globally increasing. We have previously described that glycomacropeptide (GMP), a bioactive milk peptide, has therapeutic value in experimental models of skin hypersensitivity, anaphylaxis, and asthma, as it prevents an excessive T helper type 2 cell immune response. The aim of this study was to analyze the effect of GMP on key elements directly involved in the development or control of allergy, in order to improve the precise knowledge about its mechanism of action...
January 4, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28049203/the-involvement-of-protein-kinase-d-in-t-cell-induced-mast-cell-activation
#13
Pazit Salamon, Irit Shefler, Alon Y Hershko, Yoseph A Mekori
BACKGROUND: It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation. METHODS: Human MC were stimulated by activated T cell membranes (T*m). Phosphorylation of kinases was assessed by Western blotting...
January 4, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28045928/altered-epithelial-gene-expression-in-peripheral-airways-of-severe-asthma
#14
Akul Singhania, Hitasha Rupani, Nivenka Jayasekera, Simon Lumb, Paul Hales, Neil Gozzard, Donna E Davies, Christopher H Woelk, Peter H Howarth
Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2...
2017: PloS One
https://www.readbyqxmd.com/read/28045016/the-three-herb-formula-shuang-huang-lian-stabilizes-mast-cells-through-activation-of-mitochondrial-calcium-uniporter
#15
Yuan Gao, Rui Hou, Qiaoling Fei, Lei Fang, Yixin Han, Runlan Cai, Cheng Peng, Yun Qi
Mast cells (MCs) are key effector cells of IgE-FcεRI- or MrgprX2-mediated signaling event. Shuang-Huang-Lian (SHL), a herbal formula from Chinese Pharmacopoeia, has been clinically used in type I hypersensitivity. Our previous study demonstrated that SHL exerted a non-negligible effect on MC stabilization. Herein, we sought to elucidate the molecular mechanisms of the prominent anti-allergic ability of SHL. MrgprX2- and IgE-FcεRI-mediated MC activation in vitro and in vivo models were developed by using compound 48/80 (C48/80) and shrimp tropomyosin (ST), respectively...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28044941/design-synthesis-and-biological-evaluation-of-a-phenyl-butyric-acid-derivative-n-4-chlorophenyl-4-phenylbutanamide-a-hdac6-inhibitor-with-anti-proliferative-activity-on-cervix-cancer-and-leukemia-cells
#16
Rodríguez-Fonseca Rolando Alberto, Sixto-López Yudibeth, Fragoso-Vázquez M Jonathan, Flores-Mejía Raúl, Cabrera-Pérez Laura Cristina, Vázquez-Moctezuma Ismael, Rosales-Hernández Martha Cecilia, Bello Martiniano, M Martínez-Archundia, Trujillo-Ferrara José Guadalupe, Becerra-Martínez Elvia, Correa-Basurto José
The epigenetic regulation of genes in cancer could be targeted by inhibiting Histone deacetylase 6 (HDAC6), an enzyme involved in several types of cancer such as lymphoma, leukemia, ovarian cancer, etc. Through in silico methods, a set of Phenyl butyric acid derivatives with possible HDAC6 inhibitory activity were designed, rendering monophenylamides and biphenylamides using tubacin (HDAC6 selective inhibitor) as reference. The target compounds were submitted to theoretical ADMET analyses and their binding properties on different HDAC6 conformers were evaluated through docking calculations...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28044192/porcine-mast-cells-infected-with-h1n1-influenza-virus-release-histamine-and-inflammatory-cytokines-and-chemokines
#17
In Hong Lee, Hyun Soo Kim, Sang Heui Seo
Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines...
January 2, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28039964/degenerative-joint-diseases-and-neuroinflammation
#18
REVIEW
Mariella Fusco, Stephen D Skaper, Stefano Coaccioli, Antonella Paladini, Giustino Varrassi
Rheumatic and joint diseases, as exemplified by osteoarthritis and rheumatoid arthritis, are among the most widespread painful and disabling pathologies across the globe. Given the continuing rise in life expectancy, their prevalence is destined to grow. Osteoarthritis, a degenerative joint disease, is, in particular, on its way to becoming the fourth leading cause of disability worldwide by 2020, with the rising incidence of obesity in addition to age being important factors. It is estimated that 25% of osteoarthritic individuals are unable to perform daily activities...
December 31, 2016: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28039304/allergen-valency-dose-and-fc%C3%AE%C2%B5ri-occupancy-set-thresholds-for-secretory-responses-to-pen-a-1-and-motivate-design-of-hypoallergens
#19
Avanika Mahajan, Lama A Youssef, Cédric Cleyrat, Rachel Grattan, Shayna R Lucero, Christopher P Mattison, M Frank Erasmus, Bruna Jacobson, Lydia Tapia, William S Hlavacek, Mark Schuyler, Bridget S Wilson
Ag-mediated crosslinking of IgE-FcεRI complexes activates mast cells and basophils, initiating the allergic response. Of 34 donors recruited having self-reported shrimp allergy, only 35% had significant levels of shrimp-specific IgE in serum and measurable basophil secretory responses to rPen a 1 (shrimp tropomyosin). We report that degranulation is linked to the number of FcεRI occupied with allergen-specific IgE, as well as the dose and valency of Pen a 1. Using clustered regularly interspaced palindromic repeat-based gene editing, human RBL(rαKO) cells were created that exclusively express the human FcεRIα subunit...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28038453/histone-deacetylase-inhibitor-saha-mediates-mast-cell-death-and-epigenetic-silencing-of-constitutively-active-d816v-kit-in-systemic-mastocytosis
#20
Katarina Lyberg, Hani Abdulkadir Ali, Jennine Grootens, Matilda Kjellander, Malin Tirfing, Michel Arock, Hans Hägglund, Gunnar Nilsson, Johanna Ungerstedt
Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC...
December 25, 2016: Oncotarget
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