Abstract
Mesenchymal stem cells (MSCs), derived from either bone marrow (BM) or Wharton's jelly (WJ), inhibit the proliferation of activated T cells, and interferon (IFN)-? serves an important role in this process. This process is B7-homolog (H)1-dependent during cell contact inhibition. However, the signaling pathway involved in B7-H1 expression in MSCs remains largely undefined. The present study demonstrated activation of B7-H1 by engaging signal transducer and activator of transcription (STAT)-1 signaling in MSCs. Human BM- and WJ-MSCs were isolated and cultured. The immunosuppressive effect of BM- and WJ-MSCs on phytohemagglutinin (PHA)-induced T cell proliferation was compared using direct and indirect co-culture systems. B7-H1 expression on BM- and WJ-MSCs was detected by flow cytometry. Small interfering (si)RNA was used to knock down the expression of STAT-1. The inhibitory effect of MSCs on T lymphocytes was observed using PHA-induced T cell proliferation assays. IFN-?-induced B7-H1 expression on human BM- and WJ-MSCs increased in a time-dependent manner. Furthermore, the inhibitory effect of MSCs on T cell proliferation was be restored when an anti-B7-H1 monoclonal antibody was used. When STAT-1 signaling was inhibited by siRNA, B7-H1 expression on IFN-?-treated MSCs decreased and T cell proliferation was restored; however, the expression of B7-H1 did not alter upon treatment with a phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002). These results demonstrated that the IFN-?-induced immunosuppressive properties of B7-H1 in human BM- and WJ-MSCs were mediated by STAT-1 signaling, and not by PI3K/RAC-a serine/threonine-protein kinase signaling. Understanding the intracellular mechanisms underlying IFN-?-induced expression of B7-H1 in MSCs may ultimately lead to an improved understanding of MSCs and provide insight into their use as cell therapy agents.
Original language | English |
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Pages (from-to) | 1842-1848 |
Number of pages | 7 |
Journal | Molecular Medicine Reports |
Volume | 18 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2018 Aug |
Bibliographical note
Funding Information:The authors thank the Ajou University Medical Center for funding (grant no. M-2015-C0460-00110).
Funding Information:
The authors thank the Ajou University Medical Center for funding (grant no. M‑2015‑C0460‑00110).
Publisher Copyright:
© 2018 Spandidos Publications. All rights reserved.
Keywords
- Activator of transcription 1
- B7-homolog 1
- Interferon-?
- Mesenchymal stem cells
- Phosphatidylinositol-3-kinase/RAC-a serine/threonine-protein kinase
- Signal transducer
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Genetics
- Oncology
- Cancer Research