Role of growth hormone in maturation and activation of dendritic cells via miR-200a and the Keap1/Nrf2 pathway.

Abstract

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. 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 invivo. 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. 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.