Negative regulatory roles of ORMDL3 in the Fc epsilon RI-triggered expression of proinflammatory mediators and chemotactic response in murine mast cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00471890" target="_blank" >RIV/68378050:_____/16:00471890 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1007/s00018-015-2047-3" target="_blank" >http://dx.doi.org/10.1007/s00018-015-2047-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-015-2047-3" target="_blank" >10.1007/s00018-015-2047-3</a>
Alternative languages
Result language
angličtina
Original language name
Negative regulatory roles of ORMDL3 in the Fc epsilon RI-triggered expression of proinflammatory mediators and chemotactic response in murine mast cells
Original language description
Single-nucleotide polymorphism studies have linked the chromosome 17q12-q21 region, where the human orosomucoid-like (ORMDL)3 gene is localized, to the risk of asthma and several other inflammatory diseases. Although mast cells are involved in the development of these diseases, the contribution of ORMDL3 to the mast cell physiology is unknown. In this study, we examined the role of ORMDL3 in antigen-induced activation of murine mast cells with reduced or enhanced ORMDL3 expression. Our data show that in antigen-activated mast cells, reduced expression of the ORMDL3 protein had no effect on degranulation and calcium response, but significantly enhanced phosphorylation of AKT kinase at Ser 473 followed by enhanced phosphorylation and degradation of I kappa B alpha and translocation of the NF-kappa B p65 subunit into the nucleus. These events were associated with an increased expression of proinflammatory cytokines (TNF-alpha, IL-6, and IL-13), chemokines (CCL3 and CCL4), and cyclooxygenase-2 dependent synthesis of prostaglandin D2. Antigen-mediated chemotaxis was also enhanced in ORMDL3-deficient cells, whereas spreading on fibronectin was decreased. On the other hand, increased expression of ORMDL3 had no significant effect on the studied signaling events, except for reduced antigen-mediated chemotaxis. These data were corroborated by increased IgE-antigen-dependent passive cutaneous anaphylaxis in mice with locally silenced ORMDL3 using short interfering RNAs. Our data also show that antigen triggers suppression of ORMDL3 expression in the mast cells. In summary, we provide evidence that downregulation of ORMDL3 expression in mast cells enhances AKT and NF-kappa B-directed signaling pathways and chemotaxis and contributes to the development of mast cell-mediated local inflammation in vivo.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and Molecular Life Sciences
ISSN
1420-682X
e-ISSN
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Volume of the periodical
73
Issue of the periodical within the volume
6
Country of publishing house
CH - SWITZERLAND
Number of pages
21
Pages from-to
1265-1285
UT code for WoS article
000371079200011
EID of the result in the Scopus database
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