Pentacyclic triterpenoid ursolic acid interferes with mast cell activation via a lipid-centric mechanism affecting Fc epsilon RI signalosome functions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00565125" target="_blank" >RIV/68378050:_____/22:00565125 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.jbc.2022.102497" target="_blank" >https://doi.org/10.1016/j.jbc.2022.102497</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2022.102497" target="_blank" >10.1016/j.jbc.2022.102497</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pentacyclic triterpenoid ursolic acid interferes with mast cell activation via a lipid-centric mechanism affecting Fc epsilon RI signalosome functions

Popis výsledku v původním jazyce

Pentacyclic triterpenoids, including ursolic acid (UA), are bioactive compounds with multiple biological activities involving anti-inflammatory effects. However, the mode of their action on mast cells, key players in the early stages of allergic inflammation, and underlying molecular mechanisms remain enigmatic. To better understand the effect of UA on mast cell signaling, here we examined the consequences of short-term treatment of mouse bone marrow-derived mast cells with UA. Using IgE-sensitized and antigen-or thapsigargin-activated cells, we found that 15 min exposure to UA inhibited high affinity IgE receptor (FceRI)-mediated degranulation, calcium response, and extracellular calcium uptake. We also found that UA inhibited migration of mouse bone marrow-derived mast cells toward antigen but not toward prostaglandin E2 and stem cell factor. Compared to control antigen-activated cells, UA enhanced the production of tumor necrosis factor-alpha at the mRNA and protein levels. However, secretion of this cytokine was inhibited. Further analysis showed that UA enhanced tyrosine phosphorylation of the SYK kinase and several other proteins involved in the early stages of FceRI signaling, even in the absence of antigen activation, but inhibited or reduced their further phosphorylation at later stages. In addition, we show that UA induced changes in the properties of detergent-resistant plasma membrane microdomains and reduced antibody-mediated clustering of the FceRI and glycosylphosphatidylinositol-anchored protein Thy1. Finally, UA inhibited mobility of the FceRI and cholesterol. These combined data suggest that UA exerts its effects, at least in part, via lipid-centric plasma membrane perturbations, hence affecting the functions of the FceRI signalosome.

Název v anglickém jazyce

Pentacyclic triterpenoid ursolic acid interferes with mast cell activation via a lipid-centric mechanism affecting Fc epsilon RI signalosome functions

Popis výsledku anglicky

Pentacyclic triterpenoids, including ursolic acid (UA), are bioactive compounds with multiple biological activities involving anti-inflammatory effects. However, the mode of their action on mast cells, key players in the early stages of allergic inflammation, and underlying molecular mechanisms remain enigmatic. To better understand the effect of UA on mast cell signaling, here we examined the consequences of short-term treatment of mouse bone marrow-derived mast cells with UA. Using IgE-sensitized and antigen-or thapsigargin-activated cells, we found that 15 min exposure to UA inhibited high affinity IgE receptor (FceRI)-mediated degranulation, calcium response, and extracellular calcium uptake. We also found that UA inhibited migration of mouse bone marrow-derived mast cells toward antigen but not toward prostaglandin E2 and stem cell factor. Compared to control antigen-activated cells, UA enhanced the production of tumor necrosis factor-alpha at the mRNA and protein levels. However, secretion of this cytokine was inhibited. Further analysis showed that UA enhanced tyrosine phosphorylation of the SYK kinase and several other proteins involved in the early stages of FceRI signaling, even in the absence of antigen activation, but inhibited or reduced their further phosphorylation at later stages. In addition, we show that UA induced changes in the properties of detergent-resistant plasma membrane microdomains and reduced antibody-mediated clustering of the FceRI and glycosylphosphatidylinositol-anchored protein Thy1. Finally, UA inhibited mobility of the FceRI and cholesterol. These combined data suggest that UA exerts its effects, at least in part, via lipid-centric plasma membrane perturbations, hence affecting the functions of the FceRI signalosome.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Svazek periodika

28

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

17

Strana od-do

102497

Kód UT WoS článku

000886086000009

EID výsledku v databázi Scopus

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