Qiu-Liang Liu1, Jiao Zhang1, Xin Liu1, Jing-Yao Gao1. 1. Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Abstract
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.
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 osteosarcomamouse 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.
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