title: IL-6 production stimulated by CD14(+) monocytes-paracrined IL-1β does not contribute to the immunosuppressive activity of human umbilical cord mesenchymal stem cells.
abstract: OBJECTIVE
  Human umbilical cord mesenchymal stem cells (hUC-MSCs) possess immunosuppressive activities but the mechanisms of such activities are not fully understood. Here, we investigated the role of IL-6, one of the characteristic factors of MSCs, in the immunoregulating effect of hUC-MSCs on CD4(+) T lymphocytes.
  
  
  METHODS
  The condition media from human peripheral blood mononuclear cells (hPBMCs) or CD14+/- cell were tested if stimulating IL-6 production by hUC-MSCs. The related signaling pathway of IL-6, and the immunosuppressive activity of IL-6 on CD4(+) T lymphocytes were studied.
  
  
  RESULTS
  IL-6 production was dramatically increased by hUC-MSCs when co-culturing with resting or activated hPBMCs. CD14(+) monocytes-paracrined IL-1β promoted the secretion of IL-6 by hUC-MSCs via JNK and NF-κB signaling pathway. Blocking of PGE2 synthesis did not affect the secretion of IL-6, anti-IL-6 antibody was not able to reverse hUC-MSCs-mediated inhibition on CD4(+) T lymphocytes. IL-6 did not mediate the suppressive activity of IL-1β-hUC-MSCs- PGE2 on CD4(+) T cell.
  
  
  CONCLUSIONS
  CD14(+) monocytes-paracrined IL-1β promotes IL-6 secretion by hUC-MSCs through activating JNK and NF-κB signaling pathway. However, increased IL-6 production does not contribute to immunosuppressive activity of IL-1β-hUC-MSCs- PGE2 on CD4(+) T cells.
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: Yue Ru
authors.initials: YR
authors.lastname: Ji
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Wei Ting
authors.initials: WT
authors.lastname: Du
authors.forename: Zhou Xin
authors.initials: ZX
authors.lastname: Yang
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Chi
authors.forename: Lu
authors.initials: L
authors.lastname: Liang
authors.forename: Francis
authors.initials: F
authors.lastname: Bayard
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009578:Nitrobenzenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014470:Umbilical Cord / Q000166:cytology / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; C508585:IL1B protein, human; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015232:Dinoprostone