Cytokine Production by Human Mast Cells

Okayama, Yoshimichi; Bradding, Peter; Tunon-de-Lara, José-Manuel; Holgate, S T; Mk, Church

doi:10.1159/000319282

Cited by 27 publications

(12 citation statements)

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“…and mortality of anaphylaxis and other allergic disorders by virtue of their ability to be activated through FcεRI bound antigen-specific IgE and their concentration at surfaces that interface with the external environment (Marone et al, 1999;Katz 2002). Mast cells may also be activated by various cytokines through each cytokine receptor (Okayama et al, 1995). Activation through any of these receptors leads to the release of a number of biologically active molecules through the process of exocytosis.…”

Section: Resultsmentioning

confidence: 99%

Anti-allergic activity of an ethanol extract from Salviae miltiorrhiza

Yang

Son

et al. 2008

Arch. Pharm. Res.

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As part of an ongoing investigation aimed at the discovery of novel bioactive medicinal herbs with anti-inflammatory properties, the effects of an ethanolic extract from the parts of Salviae miltiorrhiza Bunge (ESM) were evaluated using in vitro and in vivo animal model analysis. ESM inhibited cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 3.96 microg/mL and 21.54 microg/mL, respectively. Furthermore, ESM inhibited leukotriene C4 (LTC4) production with an IC50 value of 2.6 microg/mL. These results clearly demonstrated the dual COX-2 selective/5-lipoxygenase inhibitory activity that ESM possessed. ESM strongly inhibited a degranulation reaction in a dose dependent manner within a BMMC system, with an IC50 value of 22.4 microg/mL. Additionally, ESM was tested in a rat passive cutaneous anaphylaxis (PCA) reaction assay by oral administration (25 to 100 mg/kg). ESM dose-dependently inhibited the PCA reaction, which was activated by anti-dinirophenyl (DNP) IgE. These results suggested that ESM might be beneficial in regulating various allergic reactions.

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Section: Resultsmentioning

confidence: 99%

Anti-allergic activity of an ethanol extract from Salviae miltiorrhiza

Yang

Son

et al. 2008

Arch. Pharm. Res.

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“…Moreover, a guinea pig model demonstrated increased NAGA released from bronchoalveolar macrophages in animals with increased airways responsiveness following high ozone exposure 36 . Though speculative, given the central role of macrophages and mast cell degranulation in bronchoconstriction, mucus secretion, and airway inflammation in asthmatics 37 , the asthma-associated NAGA eSNP may influence asthma risk through altered glycohydrolase activity.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes

Sharma

Zhou

Thibault

et al. 2014

Journal of Allergy and Clinical Immunology

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Background Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective We evaluated 6,706 cis-acting expression-associated variants (eSNP) identified through a genome-wide eQTL survey of CD4+ lymphocytes for association with asthma. Methods eSNP were tested for association with asthma in 359 asthma cases and 846 controls from the Childhood Asthma Management Program, with verification using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE)-qPCR and Chromatin-Immunoprecipitation (ChIP)-PCR in lung derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results Cis-acting eSNP demonstrated associations with asthma in both cohorts. We confirmed the previously-reported association of ORMDL3/GSDMB variants with asthma (combined p=2.9 × 108). Reproducible associations were also observed for eSNP in three additional genes: FADS2 (p=0.002), NAGA (p=0.0002), and F13A1 (p=0.0001). We subsequently demonstrated that FADS2 mRNA is increased in CD4+ lymphocytes in asthmatics, and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes, and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.

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“…The following mouse monoclonal antibodies (MAbs) were used: anti‐CD3 (1:500; Becton‐Dickinson, Sunnyvale, CA, USA); anti‐CD68 (1:1000; Dako, Copenhagen, Denmark); anti‐tryptase (1:500; Chemicon, Temecula, CA, USA); anti‐hIL‐4 (1:500; kindly provided by C.H. Heusser, Ciba‐Geigy, Basel, Switzerland)10; and MiB‐1 (1:200; Dianova, Hamburg, Germany)11, 12. Biotin‐conjugated sheep anti‐mouse Ig (1:200; Amersham, Braunschweig, Germany) was used as the secondary antibody.…”

Section: Methodsmentioning

confidence: 99%