title: Kirenol attenuates experimental autoimmune encephalomyelitis by inhibiting differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells.
abstract: Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. Here we investigated effects of kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-γ and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced kirenol induced apoptosis. Our findings implicate kirenol as a useful agent for the treatment of MS.
authors.affiliation: 1] Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China [2] Department of Biological Treatment, Handan Central Hospital, Handan, Hebei, China [3] Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Biological Treatment, Handan Central Hospital, Handan, Hebei, China.
authors.forename: Rongbing
authors.initials: R
authors.lastname: Yang
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Fan
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: 1] Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China [2] Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007156:Immunologic Memory; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D004224:Diterpenes; D063308:Myelin-Oligodendrocyte Glycoprotein; C560087:kirenol