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

0450580 - ÚEM 2017 RIV DE eng J - Journal Article
Heřmánková, Barbora - Zajícová, Alena - Javorková, Eliška - Chudíčková, Milada - Trošan, Peter - Hájková, Michaela - Krulová, Magdaléna - Holáň, Vladimír
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.
Immunobiology. Roč. 221, č. 2 (2016), s. 129-136. ISSN 0171-2985
R&D Projects: GA MŠMT(CZ) LO1309; GA ČR(CZ) GA14-12580S; GA MZd NT14102; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:68378041
Keywords : B cells * Cyclooxygenase-2 * IL-10 production * Mesenchymal stem cells * Cyclooxygenase-2 * Immunosuppression
Subject RIV: FF - HEENT, Dentistry
Impact factor: 2.720, year: 2016

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.
Permanent Link: http://hdl.handle.net/11104/0268931