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TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs.

ABSTRACT: To the best of our knowledge, our previous study demonstrated the expression of triggering receptor expressed on myeloid cells 2 (TREM?2) in human bone marrow mesenchymal stem cells (MSCs) for the first time. However, the inflammation regulatory role of TREM?2 in MSCs remain elusive. The aim of the present study was to investigate the immune regulation and the underlying mechanism of TREM?2 in rat bone marrow MSCs. MSCs were divided into three groups: NullMSCs, TREM?2MSCs, and NormMSCs. TREM?2 was expressed in MSCs at the mRNA and protein level. Following stimulation by lipopolysaccharide (LPS), the gene transcription levels of TREM?2 and inflammatory cytokines were increased. The expression levels of inflammatory cytokines, including tumor necrosis factor?? (TNF??) and interleukin?1? (IL?1?), in the TREM?2MSCs lentiviral vector group were significantly downregulated, and the expression of IL?10 was significantly upregulated compared with the controls. Western blot analysis revealed that TREM?2 downregulated the LPS?induced inflammatory response in MSCs, which was probably associated with regulating AKT serine/threonine kinase and p38 mitogen?activated protein kinase downstream signaling proteins. The results of the current study demonstrated that TREM?2 negatively regulates the LPS?mediated inflammatory response in MSCs suggesting that TREM?2 is a potential target of immune regulation in rat MSCs.

SUBMITTER: Ye P

PROVIDER: S-EPMC5647029 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs.

Ye Pei P Xu Dawei D Xu Jinhuang J Liu Guiwang G Huang Shenghui S Zhang Weiqiong W Zheng Peizhong P Li Jianhua J Huang Jianrong J

Molecular medicine reports 20170810 4

To the best of our knowledge, our previous study demonstrated the expression of triggering receptor expressed on myeloid cells 2 (TREM‑2) in human bone marrow mesenchymal stem cells (MSCs) for the first time. However, the inflammation regulatory role of TREM‑2 in MSCs remain elusive. The aim of the present study was to investigate the immune regulation and the underlying mechanism of TREM‑2 in rat bone marrow MSCs. MSCs were divided into three groups: NullMSCs, TREM‑2MSCs, and NormMSCs. TREM‑2 w ...[more]

PMID: 28849042

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Project description:Stem cell-based therapies raise hope for cell replacement and provide opportunity for cardiac regenerative medicine and tumor therapy. Extracellular vesicles are a membrane-enclosed intercellular delivery system with the potential to improve the therapeutic efficacy of the treatment of a variety of disorders. As the incidence of breast cancer continues to rise, radiotherapy has emerged as a leading treatment modality. Radiotherapy also increases the risk of coronary heart disease and cardiac mortality. In a chest-irradiated mouse model of cardiac injury, we investigated the effects of local irradiation. We found an increased lethality after 16 Gy irradiation. Importantly, radio-detoxified LPS (RD-LPS) treatment prolonged the survival significantly. By flow cytometry, we demonstrated that upon administration of RD-LPS, the number of bone marrow-derived endothelial progenitor cells increased in the bone marrow and, in particular, in the circulation. Furthermore, mass spectrometry analysis showed that RD-LPS altered the proteomic composition of bone marrow cell-derived small extracellular vesicles (sEVs). RD-LPS treatment increased interferon-induced transmembrane protein-3 (IFITM3) expression markedly both in bone marrow cells and in bone marrow cell-derived small extracellular vesicles. This is the first study to demonstrate that radio-detoxified LPS treatment induces an increase of circulating endothelial progenitor cells (EPCs) in parallel with a reduced radiotherapy-related mortality. While the total number of bone marrow-derived extracellular vesicles was significantly increased 24 h after treatment in the RD-LPS groups, the number of endothelial progenitor cells was reduced in animals injected with GW4896 (a chemical inhibitor of exosome biogenesis) as compared with controls. In contrast to these in vivo results, in vitro experiments did not support the effect of sEVs on EPCs. Our data raise the intriguing possibility that IFITM3 may serve as a marker of the radio-detoxified LPS treatment.

Dataset Information

TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs.

Publications

TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs.

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