PMID- 26289744 OWN - NLM STAT- MEDLINE DCOM- 20151120 LR - 20200315 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 48 IP - 5 DP - 2015 Oct TI - Role of growth hormone in maturation and activation of dendritic cells via miR-200a and the Keap1/Nrf2 pathway. PG - 573-81 LID - 10.1111/cpr.12206 [doi] AB - OBJECTIVES: Dendritic cells (DCs) are antigen-presenting cells that participate in the immune response; recently, it has been reported that growth hormone (GH) promotes their maturation. The aim of this study was to investigate mechanisms by which GH acts on DC maturation and activation. MATERIALS AND METHODS: Human peripheral blood monocytes (HPBMs) were induced to become immature DCs and treated with GH to obtain mature DCs. An osteosarcoma mouse model was established by injection of LM8 cells to investigate anti-tumour effect of GH-induced DCs in vivo. RESULTS: After administration of GH, DCs reduced miR-200a expression and nuclear Nrf2 accumulation; miR-200a down-regulation inhibited DC maturation. Nrf2 ubiquitination level was increased by Keap1 overexpression in murine bone marrow derived dendritic cells (BMDCs), which was cancelled by miR-200a in GH exposed cells. In vivo, tumour volume was significantly reduced by GH-treated DCs and the effect was reversed by overexpression of miR-200a. CONCLUSIONS: GH promoted maturation and activation of DCs, and regulation of miR-200a played a part in this process by modulation of the Keap1/Nrf2 pathway. CI - (c) 2015 John Wiley & Sons Ltd. FAU - Liu, Qiu-Liang AU - Liu QL AD - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Zhang, Jiao AU - Zhang J AD - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Liu, Xin AU - Liu X AD - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Gao, Jing-Yao AU - Gao JY AD - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150820 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (3' Untranslated Regions) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (KEAP1 protein, human) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (MIRN200 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Oligonucleotides, Antisense) RN - 0 (RNA, Small Interfering) RN - 9002-72-6 (Growth Hormone) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/immunology MH - Down-Regulation/drug effects MH - Female MH - Growth Hormone/*pharmacology MH - Humans MH - Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/genetics/metabolism MH - Kelch-Like ECH-Associated Protein 1 MH - Lung Neoplasms/secondary/therapy MH - Mice MH - Mice, Inbred C3H MH - MicroRNAs/antagonists & inhibitors/genetics/*metabolism MH - NF-E2-Related Factor 2/metabolism MH - Oligonucleotides, Antisense/genetics/metabolism MH - Osteoblastoma/pathology/therapy MH - RNA, Small Interfering/genetics/metabolism MH - Signal Transduction/*drug effects MH - Transplantation, Heterologous MH - Ubiquitination/drug effects PMC - PMC6496568 COIS- All authors have no conflict of interest to state. EDAT- 2015/08/21 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/08/20 CRDT- 2015/08/21 06:00 PHST- 2015/04/28 00:00 [received] PHST- 2015/06/15 00:00 [accepted] PHST- 2015/08/21 06:00 [entrez] PHST- 2015/08/21 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/08/20 00:00 [pmc-release] AID - CPR12206 [pii] AID - 10.1111/cpr.12206 [doi] PST - ppublish SO - Cell Prolif. 2015 Oct;48(5):573-81. doi: 10.1111/cpr.12206. Epub 2015 Aug 20.