title: Sinomenine reduces iNOS expression via inhibiting the T-bet IFN-γ pathway in experimental autoimmune encephalomyelitis in rats.
abstract: Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum. It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases. In our previous studies, we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis (EAE) in rats. In this study, we further investigated the mechanisms of sinomenine treatment in EAE rats. In EAE rats, treatment with sinomenine exerted an anti-inducible NO synthase (anti-iNOS) effect, which is related to the reductions of Th1 cytokine interferon-γ (IFN-γ) and its transcription factor, T-bet, in spinal cords. Moreover, sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12 reduced the expression of T-bet and IFN-γ in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes. However, sinomenine had no direct inhibitory effect on iNOS produced by astrocytes cultured with IFN-γ and tumor necrosis factor α in vitro. In conclusion, the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-γ pathway.
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Bingjie
authors.initials: B
authors.lastname: Gu
authors.forename: Yanying
authors.initials: Y
authors.lastname: Zeng
authors.forename: Cheng
authors.initials: C
authors.lastname: Yin
authors.forename: Huijiuan
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Yang
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ji
keywords: T-bet; experimental autoimmune encephalomyelitis; iNOS; interferon-γ (IFN-γ); sinomenine
references.citation: Mol Immunol. 2008 Feb;45(4):1191-6
references.pmid: 17697713
references.citation: Cell Biol Int. 2007 Aug;31(8):784-9
references.pmid: 17383204
references.citation: Neurology. 2007 May 29;68(22 Suppl 3):S22-31; discussion S43-54
references.pmid: 17548565
references.citation: J Neurol. 2011 Oct;258(10):1747-62
references.pmid: 21637950
references.citation: Brain Res. 2000 Feb 7;855(1):39-46
references.pmid: 10650128
references.citation: J Neuroimmunol. 2005 Mar;160(1-2):110-21
references.pmid: 15710464
references.citation: NMR Biomed. 2006 Feb;19(1):101-7
references.pmid: 16411166
references.citation: Angiogenesis. 2005;8(1):3-12
references.pmid: 16132613
references.citation: Annu Rev Immunol. 2005;23:683-747
references.pmid: 15771584
references.citation: Brain. 2009 May;132(Pt 5):1175-89
references.pmid: 19339255
references.citation: Immunity. 2004 Nov;21(5):719-31
references.pmid: 15539157
references.citation: Int Immunopharmacol. 2009 Jul;9(7-8):894-9
references.pmid: 19336263
references.citation: Nat Clin Pract Neurol. 2006 Apr;2(4):201-11
references.pmid: 16932551
references.citation: Cell. 2000 Mar 17;100(6):655-69
references.pmid: 10761931
references.citation: Biol Pharm Bull. 2007 Aug;30(8):1438-44
references.pmid: 17666800
references.citation: Acta Clin Croat. 2009 Sep;48(3):349-53
references.pmid: 20055262
references.citation: J Ethnopharmacol. 2005 Apr 8;98(1-2):37-43
references.pmid: 15763362
references.citation: Lancet Neurol. 2002 Aug;1(4):232-41
references.pmid: 12849456
references.citation: Int J Immunopharmacol. 1996 Oct;18(10):529-43
references.pmid: 9080247
references.citation: FEBS Lett. 2011 Dec 1;585(23):3747-57
references.pmid: 21477588
references.citation: Biochem Biophys Res Commun. 2010 Jan 1;391(1):1093-8
references.pmid: 20004644
references.citation: Immunol Lett. 2005 Apr 15;98(1):91-6
references.pmid: 15790513
references.citation: Autoimmunity. 2007 Nov;40(7):532-9
references.pmid: 17966044
references.citation: Brain. 2006 Aug;129(Pt 8):1953-71
references.pmid: 16632554
references.citation: J Cell Sci. 2004 Jun 15;117(Pt 14):2865-7
references.pmid: 15197240
references.citation: Brain Res Mol Brain Res. 2002 Feb 28;99(1):17-25
references.pmid: 11869804
references.citation: J Exp Med. 2009 Jul 6;206(7):1549-64
references.pmid: 19546248
references.citation: Neurochem Int. 2006 Jul;49(2):154-63
references.pmid: 16740341