title: [Synergistic immunomodulatory effects of interferon-gamma and bone marrow mesenchymal stem cells].
abstract: OBJECTIVE
  To investigate mesenchymal stem cells (MSCs) immunosuppressive activity in the presence of interferon-gamma (IFN-γ) to reveal synergistic immunomodulatory effects of IFN-γ and MSCs.
  
  
  METHODS
  ① MSCs were cultured in the presence or absence of IFN-γ（100 ng/ml）, the supernatants were collected for measurements of PGE2、HGF and TGF-β1 by ELISA kits. ② MSCs were cultured in the presence or absence of IFN-γ （100 ng/ml）for 48 h. The cDNA was analysed for the expression of human indoleamine 2, 3-dioxygenase（IDO）mRNA by semiquantitative RT-PCR. ③ Mononuclear cells (MNCs) were extracted from peripheral blood of healthy donors. The T cell proliferation was tested in the co-culture system added with MSCs, recombinant human IFN-γ (100 ng/ml) and anti-IFN-γ mAb (5 μg/ml) by BrdU ELISA kit.
  
  
  RESULTS
  ①The immunosuppressive cytokines PGE2、HGF and TGF-β1 were detectable within 24-48 h in the supernatants. Their expressions were significantly up-regulated in the presence of IFN-γ. Concentrations of these cytokines were as of (1715.5±628.6) pg/ml vs (1344.5±709.4) pg/ml (P=0.001);(4031.8±1496.8) pg/ml vs (2452.4±1375.3) pg/ml（P=0.011）;(1753.5±413.8) pg/ml vs (1026.6±450.5) pg/ml（P<0.001）,respectively. ②The expression of IDO mRNA was undetectable when MSCs were cultured alone. In contrast, The IDO mRNA expression was remarkably enhanced in the presence of IFN-γ. ③Bone marrow-derived MSCs remarkably suppressed allogeneic T cell proliferation in vitro. Addition of exogenous IFN-γ had no significant effect on the inhibitory capacity of MSCs, the inhibitory ratios of T cell proliferation were （40.4±10.9）% vs（36.7±7.4）% (P=0.272). By contrast, the inhibitory ratio of T cell proliferation was significantly decreased in the presence of anti-IFN-γ mAb[(40.4±10.9)% vs (23.9±7.6)%,P=0.002].
  
  
  CONCLUSIONS
  ①Human MSCs constitutively expressed immunosuppressive concentrations of PGE2, HGF and TGF-β1, and their expressions were significantly up-regulated by IFN-γ. ②IFN-γ-induced expression of IDO on MSCs involved in tryptophan catabolism. ③MSCs notably suppressed allogeneic T cell proliferation in vitro. IFN-γ promoted the immunosuppressive capacity of human MSCs, indicating the synergistic immunomodulatory effect of IFN-γ and MSCs.
authors.affiliation: Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin,China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Shu-lian
authors.initials: SL
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Zhai
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ai-ming
authors.initials: AM
authors.lastname: Pang
authors.forename: Si-zhou
authors.initials: SZ
authors.lastname: Feng
authors.forename: Ming-zhe
authors.initials: MZ
authors.lastname: Han
mesh_terms: D001854:Bone Marrow Cells / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D016207:Cytokines; D007371:Interferon-gamma