PMID- 22508062 OWN - NLM STAT- MEDLINE DCOM- 20120809 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 29 IP - 3-4 DP - 2012 TI - IL-6 production stimulated by CD14(+) monocytes-paracrined IL-1beta does not contribute to the immunosuppressive activity of human umbilical cord mesenchymal stem cells. PG - 551-60 LID - 10.1159/000338509 [doi] AB - BACKGROUND/AIMS: 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. RESULT: IL-6 production was dramatically increased by hUC-MSCs when co-culturing with resting or activated hPBMCs. CD14(+) monocytes-paracrined IL-1beta promoted the secretion of IL-6 by hUC-MSCs via JNK and NF-kappaB 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-1beta-hUC-MSCs- PGE2 on CD4(+) T cell. CONCLUSION: CD14(+) monocytes-paracrined IL-1beta promotes IL-6 secretion by hUC-MSCs through activating JNK and NF-kappaB signaling pathway. However, increased IL-6 production does not contribute to immunosuppressive activity of IL-1beta-hUC-MSCs- PGE2 on CD4(+) T cells. CI - Copyright (c) 2012 S. Karger AG, Basel. FAU - Wang, Ding AU - Wang D AD - 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. FAU - Ji, Yue Ru AU - Ji YR FAU - Chen, Ke AU - Chen K FAU - Du, Wei Ting AU - Du WT FAU - Yang, Zhou Xin AU - Yang ZX FAU - Han, Zhi-Bo AU - Han ZB FAU - Chi, Ying AU - Chi Y FAU - Liang, Lu AU - Liang L FAU - Bayard, Francis AU - Bayard F FAU - Han, Zhong Chao AU - Han ZC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120403 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Culture Media, Conditioned) RN - 0 (IL1B protein, human) RN - 0 (IL6 protein, human) RN - 0 (Immunosuppressive Agents) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Nitrobenzenes) RN - 0 (Sulfonamides) RN - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - CD4-Positive T-Lymphocytes/drug effects/*immunology MH - Cell Differentiation MH - Cells, Cultured MH - Coculture Techniques MH - Culture Media, Conditioned MH - Dinoprostone/antagonists & inhibitors/immunology/pharmacology MH - Humans MH - Immunophenotyping MH - Immunosuppressive Agents/immunology/*pharmacology MH - Interleukin-1beta/*immunology/metabolism/pharmacology MH - Interleukin-6/*immunology/metabolism/pharmacology MH - Leukocytes, Mononuclear/*immunology MH - Lipopolysaccharide Receptors/immunology MH - MAP Kinase Signaling System MH - Macrophage Activation MH - Mesenchymal Stem Cells/*immunology MH - Nitrobenzenes/pharmacology MH - Sulfonamides/pharmacology MH - Umbilical Cord/cytology/immunology EDAT- 2012/04/18 06:00 MHDA- 2012/08/10 06:00 CRDT- 2012/04/18 06:00 PHST- 2012/02/02 00:00 [accepted] PHST- 2012/04/18 06:00 [entrez] PHST- 2012/04/18 06:00 [pubmed] PHST- 2012/08/10 06:00 [medline] AID - 000338509 [pii] AID - 10.1159/000338509 [doi] PST - ppublish SO - Cell Physiol Biochem. 2012;29(3-4):551-60. doi: 10.1159/000338509. Epub 2012 Apr 3.