title: Methionine enkephalin regulates microglia polarization and function.
abstract: Methionine enkephalin (MENK), an opioid peptide, is known to function as a regulator in the immune system. As microglia are considered the most important immune cells in the central nervous system (CNS), we aimed to assess the function of MENK on microglia polarization and tumoricidal responses. Initially, we chose the most optimal condition of 10-12M for 48h; however, MENK had no function on the viability and apoptosis of microglia under this treatment. However, MENK treatment markedly increased levels of M1-associated genes, such as CD86, CD40, IL-12, and TNF-α, but had no effect on M2 markers, including CD163, IL-10, and TGF-β. Moreover, microglia in the MENK-treated group showed high phagocytosis capacity, which coincided with characteristics of M1 microglia. MENK stimulation also induced up-regulation of reactive oxygen species (ROS) expression, which contributed to maintaining homeostasis. We also detected NO production by measuring the end product nitrite, and found that MENK treatment increased expression of nitrite and inducible NO synthase (iNOS), but did not influence arginase-1 (Arg1) expression. Furthermore, treatment of microglia with MENK led to a significant increase in cytotoxicity against glioblastoma cells, indicating that MENK possessed anti-tumor ability. Overall, MENK treatment could induce microglia to an M1 phenotype, modulating Th1 responses in the immune system. Additionally, microglia treated with MENK had tumoricidal activity, which provides new insight into anti-tumor immunity.
authors: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors: Xuxu
authors: X
authors: Xu
authors: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors: Yan
authors: Y
authors: Gao
authors: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors: Lulu
authors: L
authors: Wen
authors: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors: Zhiyong
authors: Z
authors: Zhai
authors: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors: Shuo
authors: S
authors: Zhang
authors: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang 110000, PR China.
authors: Fengping
authors: F
authors: Shan
authors: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China. Electronic address: cmufengjuan@sina.com.
authors: Juan
authors: J
authors: Feng
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001119:Arginase / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D005909:Glioblastoma; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D017382:Reactive Oxygen Species; D004744:Enkephalin, Methionine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C574619:ARG1 protein, human; D001119:Arginase
keywords: Anti-tumor immunity; Methionine enkephalin; Microglia; Polarization