Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-γ-treated mesenchymal stem cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F16%3A00450580" target="_blank" >RIV/68378041:_____/16:00450580 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/16:10315743

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.imbio.2015.09.017" target="_blank" >http://dx.doi.org/10.1016/j.imbio.2015.09.017</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.imbio.2015.09.017" target="_blank" >10.1016/j.imbio.2015.09.017</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-γ-treated mesenchymal stem cells

Popis výsledku v původním jazyce

The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well documented in various models in vitro and in vivo. Furthermore, a population of regulatory B cells (Bregs) that produce relatively high concentrations of IL-10 has been recently described. To study the relationship between MSCs and Bregs, we analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)-activated mouse B cells. The production of IL-10 by B cells remained preserved in the presence of MSCs and was even significantly enhanced by IFN-gamma. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-gamma. Preincubation of MSCs, but not of B cells, with IFN-gamma induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-gamma-treated MSCs had no inhibitory effect, and the suppression of IL-10 production was abrogated if the MSCs and B cells were separated in a transwell system. Analysis of the gene expression of IFN-gamma- or IFN-gamma and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IM), cyclooxygenase-2 (Cox-2) and programmed cell death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of the neutralization monoclonal antibody anti-PD-L1 did not abrogate the suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC-mediated suppression of IL-10 production. Accordingly, the production of IL-10 by B cells was inhibited by exogenous prostaglandin E-2. The results thus suggest that IFN-gamma-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway. (C) 2015 Elsevier GmbH. All rights reserved.

Název v anglickém jazyce

Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-γ-treated mesenchymal stem cells

Popis výsledku anglicky

The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well documented in various models in vitro and in vivo. Furthermore, a population of regulatory B cells (Bregs) that produce relatively high concentrations of IL-10 has been recently described. To study the relationship between MSCs and Bregs, we analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)-activated mouse B cells. The production of IL-10 by B cells remained preserved in the presence of MSCs and was even significantly enhanced by IFN-gamma. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-gamma. Preincubation of MSCs, but not of B cells, with IFN-gamma induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-gamma-treated MSCs had no inhibitory effect, and the suppression of IL-10 production was abrogated if the MSCs and B cells were separated in a transwell system. Analysis of the gene expression of IFN-gamma- or IFN-gamma and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IM), cyclooxygenase-2 (Cox-2) and programmed cell death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of the neutralization monoclonal antibody anti-PD-L1 did not abrogate the suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC-mediated suppression of IL-10 production. Accordingly, the production of IL-10 by B cells was inhibited by exogenous prostaglandin E-2. The results thus suggest that IFN-gamma-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway. (C) 2015 Elsevier GmbH. All rights reserved.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FF - ORL, oftalmologie, stomatologie

OECD FORD obor

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Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Immunobiology

ISSN

0171-2985

e-ISSN

—

Svazek periodika

221

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

8

Strana od-do

129-136

Kód UT WoS článku

000369046700001

EID výsledku v databázi Scopus

2-s2.0-84989790738