Insulin Mediates Lipopolysaccharide-Induced Inflammatory Responses and Oxidative Stress in BV2 Microglia

Abstract

Chi-Chen Huang,1 Sheng-Feng Tsai,2,3 Shu-Cheng Liu,4 Mei-Chen Yeh,5 Hao-Chang Hung,5 Chu-Wan Lee,6 Ching-Li Cheng,6 Pei-Ling Hsu,7– 9 Yu-Min Kuo2,3 1Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 2Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 3Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 4Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 71004, Taiwan; 6Department of Nursing, National Tainan Junior College of Nursing, Tainan, 700007, Taiwan; 7Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 8Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan; 9Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 80708, TaiwanCorrespondence: Pei-Ling Hsu, Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, 80708, Tel [phone] ext. 2144#16, Fax [phone], Email [email protected] Yu-Min Kuo, Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, 1 Ta Hsueh Road, Tainan, 70101, Taiwan, Tel [phone] ext. 5294, Fax [phone], Email [email protected]: Insulin, the key hormone for glucose regulation, has garnered attention for its role as an immune modulator. Impaired insulin signaling in the central nervous system is linked to neuroinflammation and neurodegenerative diseases. Microglia, the resident macrophage-like immune cells in the brain, are key regulators of neuroinflammation. However, the mechanisms by which insulin influences microglial immune responses remain relatively unknown.Methods: This study aimed to assess the effects of post-treatment with insulin [30 minutes after lipopolysaccharide (LPS) exposure] on LPS-induced inflammatory responses in BV2 microglial cells.Results: Post-treatment with insulin potentiated LPS-induced production of nitric oxide and pro-inflammatory cytokines, such as TNF and IL-6, through activation of the Akt/NF-κB pathway. Insulin also enhanced the ability of BV2 cells to phagocytose bacteria particles and β-amyloid fibrils. Conversely, insulin inhibited activation of NADPH oxidase and reduced intracellular levels of reactive oxygen species in LPS-treated BV2 cells.Conclusion: Insulin enhances microglial immune competence when challenged by endotoxins but mitigates oxidative stress in these cells. Keywords: β-amyloid, p47phox, phagocytosis, superoxide dismutase

Keywords

• β-amyloid
• p47phox
• phagocytosis
• superoxide dismutase