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
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26416211
DOI
10.1016/j.imbio.2015.09.017
PII: S0171-2985(15)30068-1
Knihovny.cz E-resources
- Keywords
- B cells, Cyclooxygenase-2, IL-10 production, Immunosuppression, Mesenchymal stem cells,
- MeSH
- Lymphocyte Activation drug effects MeSH
- B7-H1 Antigen antagonists & inhibitors genetics immunology MeSH
- B-Lymphocytes cytology drug effects immunology MeSH
- Cyclooxygenase 2 genetics immunology MeSH
- Diffusion Chambers, Culture MeSH
- Dinoprostone pharmacology MeSH
- Indoleamine-Pyrrole 2,3,-Dioxygenase genetics immunology MeSH
- Indomethacin pharmacology MeSH
- Cyclooxygenase Inhibitors pharmacology MeSH
- Interferon-gamma pharmacology MeSH
- Interleukin-10 antagonists & inhibitors genetics immunology MeSH
- Coculture Techniques MeSH
- Culture Media, Conditioned pharmacology MeSH
- Lipopolysaccharides pharmacology MeSH
- Mesenchymal Stem Cells cytology drug effects immunology MeSH
- Cell Communication immunology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Antibodies, Neutralizing pharmacology MeSH
- Primary Cell Culture MeSH
- Gene Expression Regulation MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- B7-H1 Antigen MeSH
- Cd274 protein, mouse MeSH Browser
- Cyclooxygenase 2 MeSH
- Dinoprostone MeSH
- IL10 protein, mouse MeSH Browser
- Indoleamine-Pyrrole 2,3,-Dioxygenase MeSH
- Indomethacin MeSH
- Cyclooxygenase Inhibitors MeSH
- Interferon-gamma MeSH
- Interleukin-10 MeSH
- Culture Media, Conditioned MeSH
- Lipopolysaccharides MeSH
- Antibodies, Neutralizing MeSH
- Ptgs2 protein, mouse MeSH Browser
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.
References provided by Crossref.org
Distinct Immunoregulatory Mechanisms in Mesenchymal Stem Cells: Role of the Cytokine Environment
