title: S-methylisothiourea induces apoptosis of herpes simplex virus-1-infected microglial cells.
abstract: 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.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Yuan-Jin
authors.initials: YJ
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Dong
authors.forename: Yuan-Wu
authors.initials: YW
authors.lastname: Mei
mesh_terms: 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
chemical_list: 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
references.citation: Adv Exp Med Biol. 2008;609:216-32
references.pmid: 18193668
references.citation: Neuropsychol Rehabil. 2007 Aug-Oct;17(4-5):429-49
references.pmid: 17676529
references.citation: Eur J Paediatr Neurol. 2008 Mar;12(2):72-81
references.pmid: 17870623
references.citation: Virology. 1999 Apr 10;256(2):203-12
references.pmid: 10191185
references.citation: J Exp Med. 2005 Dec 5;202(11):1459-63
references.pmid: 16330811
references.citation: Am J Surg. 2004 Jan;187(1):93-7
references.pmid: 14706594
references.citation: Neurosci Lett. 2008 Nov 7;445(1):18-22
references.pmid: 18782601
references.citation: Immunopharmacol Immunotoxicol. 2008;30(1):135-51
references.pmid: 18306110
references.citation: Glia. 2004 Sep;47(4):358-66
references.pmid: 15293233
references.citation: Methods Mol Biol. 2008;414:47-56
references.pmid: 18175811
references.citation: Herpes. 2007 Jun;14(1):11-6
references.pmid: 17848213
references.citation: Best Pract Res Clin Rheumatol. 2008 Oct;22(5):811-29
references.pmid: 19028365
references.citation: Heart Fail Rev. 2008 Jun;13(2):111-9
references.pmid: 18080749
references.citation: Int Immunopharmacol. 2008 Jul;8(7):1059-64
references.pmid: 18486919
references.citation: Nat Rev Microbiol. 2009 Feb;7(2):144-55
references.pmid: 19148180
references.citation: Ann N Y Acad Sci. 2003 Dec;1010:186-94
references.pmid: 15033718
references.citation: Cancer Lett. 2009 Aug 28;281(2):128-33
references.pmid: 19111387
references.citation: Rev Neurol Dis. 2004 Fall;1(4):169-78
references.pmid: 16400278
references.citation: Acta Biochim Biophys Sin (Shanghai). 2005 Nov;37(11):719-27
references.pmid: 16270150
references.citation: Int J Pediatr Otorhinolaryngol. 2008 Aug;72(8):1241-50
references.pmid: 18573544
references.citation: Neurosci Lett. 1999 Apr 2;264(1-3):129-32
references.pmid: 10320031
references.citation: Nitric Oxide. 2010 Jan 1;22(1):1-10
references.pmid: 19836458
references.citation: Evid Based Complement Alternat Med. 2010 Mar;7(1):97-106
references.pmid: 18955281
references.citation: Eur J Pharmacol. 2010 Jun 10;635(1-3):79-86
references.pmid: 20338162
references.citation: Methods. 2008 Mar;44(3):262-72
references.pmid: 18314058
references.citation: Eur J Pharmacol. 2008 Aug 20;590(1-3):377-86
references.pmid: 18590720
references.citation: Curr Mol Med. 2008 Aug;8(5):437-45
references.pmid: 18691071
references.citation: J Immunol. 2008 Nov 1;181(9):6417-26
references.pmid: 18941232
references.citation: Immunol Invest. 2008;37(4):339-57
references.pmid: 18569074
references.citation: Intensive Care Med. 2000 Jan;26(1):117-24
references.pmid: 10663292
references.citation: Inflammation. 2007 Dec;30(6):213-23
references.pmid: 17763929
references.citation: Drug Des Devel Ther. 2009 Dec 29;3:289-94
references.pmid: 20054446
references.citation: Indian J Med Microbiol. 2001 Jul-Sep;19(3):127-31
references.pmid: 17664814
references.citation: J Neurovirol. 2008 May;14(3):229-38
references.pmid: 18569457
references.citation: Nat Rev Mol Cell Biol. 2007 May;8(5):405-13
references.pmid: 17377525