Počet záznamů: 1
ORMDL2 Deficiency Potentiates the ORMDL3-Dependent Changes in Mast Cell Signaling
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SYSNO ASEP 0544782 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název ORMDL2 Deficiency Potentiates the ORMDL3-Dependent Changes in Mast Cell Signaling Tvůrce(i) Bugajev, Viktor (UMG-J) RID
Hálová, Ivana (UMG-J) RID, ORCID
Demková, Lívia (UMG-J)
Černohouzová, Sára (UMG-J)
Vávrová, Petra (UMG-J)
Mrkáček, Michal (UMG-J)
Utekal, Pavol (UMG-J)
Dráberová, Lubica (UMG-J) RID
Kuchař, L. (CZ)
Schuster, Bjorn (UMG-J)
Dráber, Petr (UMG-J) RIDCelkový počet autorů 11 Číslo článku 591975 Zdroj.dok. Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 11, February (2021)Poč.str. 17 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova mast cells ; passive systemic anaphylaxis ; Fcϵ ; ri ; sphingolipids ; ORMDL family ; sphingosine-1-phosphate ; passive cutaneous anaphylactic reaction Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Immunology CEP GA17-20915S GA ČR - Grantová agentura ČR GA18-18521S GA ČR - Grantová agentura ČR GA20-16481S GA ČR - Grantová agentura ČR ED2.1.00/19.0395 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LM2018126 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF18_046/0015861 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000621390600001 DOI 10.3389/fimmu.2020.591975 Anotace The systemic anaphylactic reaction is a life-threatening allergic response initiated by activated mast cells. Sphingolipids are an essential player in the development and attenuation of this response. De novo synthesis of sphingolipids in mammalian cells is inhibited by the family of three ORMDL proteins (ORMDL1, 2, and 3). However, the cell and tissue-specific functions of ORMDL proteins in mast cell signaling are poorly understood. This study aimed to determine cross-talk of ORMDL2 and ORMDL3 proteins in IgE-mediated responses. To this end, we prepared mice with whole-body knockout (KO) of Ormdl2 and/or Ormdl3 genes and studied their role in mast cell-dependent activation events in vitro and in vivo. We found that the absence of ORMDL3 in bone marrow-derived mast cells (BMMCs) increased the levels of cellular sphingolipids. Such an increase was further raised by simultaneous ORMDL2 deficiency, which alone had no effect on sphingolipid levels. Cells with double ORMDL2 and ORMDL3 KO exhibited increased intracellular levels of sphingosine-1-phosphate (S1P). Furthermore, we found that concurrent ORMDL2 and ORMDL3 deficiency increased I kappa B-alpha phosphorylation, degranulation, and production of IL-4, IL-6, and TNF-alpha cytokines in antigen-activated mast cells. Interestingly, the chemotaxis towards antigen was increased in all mutant cell types analyzed. Experiments in vivo showed that passive cutaneous anaphylaxis (PCA), which is initiated by mast cell activation, was increased only in ORMDL2,3 double KO mice, supporting our in vitro observations with mast cells. On the other hand, ORMDL3 KO and ORMDL2,3 double KO mice showed faster recovery from passive systemic anaphylaxis, which could be mediated by increased levels of blood S1P presented in such mice. Our findings demonstrate that Ormdl2 deficiency potentiates the ORMDL3-dependent changes in mast cell signaling. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2022 Elektronická adresa https://www.frontiersin.org/articles/10.3389/fimmu.2020.591975/full
Počet záznamů: 1