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
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26416211
DOI
10.1016/j.imbio.2015.09.017
PII: S0171-2985(15)30068-1
Knihovny.cz E-zdroje
- Klíčová slova
- B cells, Cyclooxygenase-2, IL-10 production, Immunosuppression, Mesenchymal stem cells,
- MeSH
- aktivace lymfocytů účinky léků MeSH
- antigeny CD274 antagonisté a inhibitory genetika imunologie MeSH
- B-lymfocyty cytologie účinky léků imunologie MeSH
- cyklooxygenasa 2 genetika imunologie MeSH
- difuzní komory kultivační MeSH
- dinoproston farmakologie MeSH
- indolamin-2,3,-dioxygenasa genetika imunologie MeSH
- indomethacin farmakologie MeSH
- inhibitory cyklooxygenasy farmakologie MeSH
- interferon gama farmakologie MeSH
- interleukin-10 antagonisté a inhibitory genetika imunologie MeSH
- kokultivační techniky MeSH
- kultivační média speciální farmakologie MeSH
- lipopolysacharidy farmakologie MeSH
- mezenchymální kmenové buňky cytologie účinky léků imunologie MeSH
- mezibuněčná komunikace imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- neutralizující protilátky farmakologie MeSH
- primární buněčná kultura MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD274 MeSH
- Cd274 protein, mouse MeSH Prohlížeč
- cyklooxygenasa 2 MeSH
- dinoproston MeSH
- IL10 protein, mouse MeSH Prohlížeč
- indolamin-2,3,-dioxygenasa MeSH
- indomethacin MeSH
- inhibitory cyklooxygenasy MeSH
- interferon gama MeSH
- interleukin-10 MeSH
- kultivační média speciální MeSH
- lipopolysacharidy MeSH
- neutralizující protilátky MeSH
- Ptgs2 protein, mouse MeSH Prohlížeč
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-γ. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-γ. Preincubation of MSCs, but not of B cells, with IFN-γ induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-γ-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-γ- or IFN-γ and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IDO), 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 E2. The results thus suggest that IFN-γ-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway.
Citace poskytuje Crossref.org
Distinct Immunoregulatory Mechanisms in Mesenchymal Stem Cells: Role of the Cytokine Environment
