Abstract
Objective To explore the mechanism of anti-injury effects of human bone marrow mesenchymal stem cells on interstitial pulmonary fibrosis. Methods Natural killer T cell (NKT cell) was induced in vitro to simulate the inflammatory characteristics of interstitial pulmonary fibrosis. Peripheral blood mononuclcar cells (PBMC) were cultured with addition of interferon-γ (IFN-γ),CD3 antibody and interleukin-2 to contain high proportion of CD3+ CD56+ NKT cell,which was collected and cultured with human bone marrow mesenchymal stem cells. The cultured supernatants were harvested and NKT phenotype was identified by flow cytometry. The levels of transforming growth factor-β1 (TGF-β1 ) and interferon-inducible protein-10 (IP-10) in supernatants were detected by enzyme linked immunosorbent assay. The levels of IFN-γ and tumor necrosis factor α (TNF-α) were detected by liquid chip technique. CD3+ CD56+ NKT cell was cultured with human bone marrow mesenchymal stem cells and then co-cultured with 16HBE for four hours. The cell survival counting of 16HBE was detected by CCK8 assay. Results Mesenchymal stem cells had immunomodulatory effects on T lymphocyte subsets including CD3+ CD56+ NKT cell,reduced CD3+ CD56+ NKT cell in peripheral blood monouclear cells,induced differentiation of regulatory T cell,and reduced the levels of IFN-γ,TNF-α and other inflammatory cytokines. After co-cultured with mesenchymal stem cells,CD3+ CD56+ NKT cell decreased from (20. 33±1. 05)%to (15.17±1.75)%( P <0. 05). Secreting high levels of TGF-β1 and IP-10 was an important molecular basis of immunomodulation of mesenchymal stem cells. Mesenchymal stem cells relieved NKT cell-mediated damage of lung epithelial cells. Conclusions Mesenchymal stem cells have immunomodulatory effects on T lymphocyte subsets including CD3+ CD56+ NKT cell,and play a protective role in killing lung epithelial cells mediated by NKT cell. Key words: Pulmonary fibrosis; Natural killer T cell; Mesenchymal stem cell; Immunomodulation
Published Version
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