Charles University, Czech Republic
Title: Up-regulation of Cox 2 pathway in interferon-γ treated mesenchymal stem cells suppress interleukin-10 production by activated B cells
Biography: Barbora Hermankova
Mesenchymal stem cells (MSCs) are a good candidate for regenerative medicine and treatment of various diseases. They are able to suppress immune response by a cell contact, production of soluble factors and by other mechanisms. In this study we analyzed the effects of mouse bone marrow-derived MSCs on IL-10 production by lipopolysaccharide (LPS) activated B cells. The production of IL‑10 by B cells was significantly enhanced in the presence of IFN-γ. Untreated MSCs had no significant effect on IL-10 production by B cells. However, when B cells were co-cultured with MSCs and IFN-γ, the production of IL-10 was strongly suppressed. Moreover, a similar effect was observed when MSCs were pre-incubated with IFN-γ and then co-cultured with activated B cells. On the other hand, the production of IL‑10 was unchanged after cultivation IFN-γ pre-treated B cells with MSCs. A strong up-regulation of genes for indoleamine‑2,3‑dioxygenase (IDO), cyclooxygenase 2 (COX-2) and programmed cell death ligand-1 (PD-L1) was detected in MSCs treated with IFN‑γ. To identify the molecule which is responsible for the suppression of IL-10 production, we used neutralization monoclonal antibody anti‑PD‑L1 or inhibitors of IDO and COX-2. The suppression of IL-10 production was abrogated only in cultures with inhibitor of COX-2. The suppressor effect of COX-2 involving pathway was verified by adding prostaglandin E2 (PGE2) to the cultures with activated B cells. The mechanism of MSC mediated inhibition of IL-10 production by LPS-activated B cells requires a direct contact between B cells and MSCs and involves COX-2 pathway leading to the production of inhibitory PGE2.