S-methylisothiourea induces apoptosis of herpes simplex virus-1-infected microglial cells.
Our study showed that S-methylisothiourea (SMT) had anti-inflammatory effects in treating herpes simplex encephalitis in mice, and SMT also induced apoptosis of herpes simplex virus (HSV-1)-infected microglial cells. Both animal and cell models were employed in this study. Both models included the following five groups: a normal control group, a virus group (HSV-1 infected), an SMT group (HSV-1-infected + SMT (0.1 mg/10 g)), a dexamethasone group (HSV-1 infected + dexamethasone (2 μg/10 g)), and an APS group (HSV-1-infected + APS (0.8 mg/10 g)). ELISA was used to measure tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10, and Greiss method was used for measuring nitric oxide (NO) secretion. HE staining was performed for detecting changes in mice brain. Flow cytometry assay for caspase-3, caspase-8, caspase-9, and caspase-12 expressions was also carried out to assess apoptosis. Expressions of TNF-α, IL-1β, and NO were significantly elevated after stimulation of microglial cells with HSV-1. Following SMT intervention, TNF-α, IL-1β, and NO levels were significantly decreased. The inflammatory changes in HSV-1-infected murine brain tissues were also reduced. SMT induction of apoptosis of HSV-stimulated microglia seemed to be through three pathways: the death receptor, mitochondrially gated, and endoplasmic reticulum. SMT can reduce HSV-induced inflammatory insult to the brain. Its mechanism of action is most probably due to the induction of microglial cell apoptosis.
Guo
Yuan-Jin
YJ
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Li
Wei
W
Li
Xiao-Feng
XF
Zhao
Lei
L
Zhang
Shu-Ling
SL
Zhou
Yu
Y
Dong
Ji-Hua
JH
Mei
Yuan-Wu
YW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; C556062:IL10 protein, mouse; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; D020169:Caspases; C027744:S-methylisothiopseudouronium
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