Multiple functional therapeutic effects of TnP: A small stable synthetic peptide derived from fish venom in a mouse model of multiple sclerosis

被引:17
作者
Komegae, Evilin Naname [1 ]
Matozo Souza, Tais Aparecida [1 ]
Grund, Lidiane Zito [1 ]
Lima, Carla [1 ]
Lopes-Ferreira, Monica [1 ]
机构
[1] Butantan Inst, Special Lab Appl Toxinol, Immunoregulat Unit, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CUPRIZONE-INDUCED DEMYELINATION; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; BLOOD-BRAIN-BARRIER; T-CELLS; CNS DEMYELINATION; NITRIC-OXIDE; DISEASE; IL-10;
D O I
10.1371/journal.pone.0171796
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The pathological condition of multiple sclerosis (MS) relies on innate and adaptive immunity. New types of agents that beneficially modify the course of MS, stopping the progression and repairing the damage appear promising. Here, we studied TnP, a small stable synthetic peptide derived from fish venom in the control of inflammation and demyelination in experimental autoimmune encephalomyelitis as prophylactic treatment. TnP decreased the number of the perivascular infiltrates in spinal cord, and the activity of MMP-9 by F4/80+ macrophages were decreased after different regimen treatments. TnP reduces in the central nervous system the infiltration of IFN-gamma-producing Th1 and IL-17A-producing Th17 cells. Also, treatment with therapeutic TnP promotes the emergence of functional Treg in the central nervous system entirely dependent on IL-10. Therapeutic TnP treatment accelerates the remyelination process in a cuprizone model of demyelination. These findings support the beneficial effects of TnP and provides a new therapeutic opportunity for the treatment of MS.
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页数:28
相关论文
共 49 条
[1]  
Adam EH, 2010, PLOS ONE, V5, DOI [10.1371/journal.pone.0012496, DOI 10.1371/JOURNAL.PONE.0012496]
[2]   T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis [J].
Axtell, Robert C. ;
de Jong, Brigit A. ;
Boniface, Katia ;
van der Voort, Laura F. ;
Bhat, Roopa ;
De Sarno, Patrizia ;
Naves, Rodrigo ;
Han, May ;
Zhong, Franklin ;
Castellanos, Jim G. ;
Mair, Robert ;
Christakos, Athena ;
Kolkowitz, Ilan ;
Katz, Liat ;
Killestein, Joep ;
Polman, Chris H. ;
Malefyt, Rene de Waal ;
Steinman, Lawrence ;
Raman, Chander .
NATURE MEDICINE, 2010, 16 (04) :406-U21
[3]   The origin and application of experimental autoimmune encephalomyelitis [J].
Baxter, Alan G. .
NATURE REVIEWS IMMUNOLOGY, 2007, 7 (11) :904-912
[4]   IL-17-producing human peripheral regulatory T cells retain suppressive function [J].
Beriou, Gaelle ;
Costantino, Cristina M. ;
Ashley, Charles W. ;
Yang, Li ;
Kuchroo, Vijay K. ;
Baecher-Allan, Clare ;
Hafler, David A. .
BLOOD, 2009, 113 (18) :4240-4249
[5]  
Bettelli E, 1998, J IMMUNOL, V161, P3299
[6]   Prospective study on the relationship between infections and multiple sclerosis exacerbations [J].
Buljevac, D ;
Flack, HZ ;
Hop, WCJ ;
Hijdra, D ;
Laman, JD ;
Savelkoul, HFJ ;
van der Meché, FGA ;
van Doorn, PA ;
Hintzen, RQ .
BRAIN, 2002, 125 :952-960
[7]   Targeted depletion of lymphotoxin-α-expressing TH1 and TH17 cells inhibits autoimmune disease [J].
Chiang, Eugene Y. ;
Kolumam, Ganesh A. ;
Yu, Xin ;
Francesco, Michelle ;
Ivelja, Sinisa ;
Peng, Ivan ;
Gribling, Peter ;
Shu, Jean ;
Lee, Wyne P. ;
Refino, Canio J. ;
Balazs, Mercedesz ;
Paler-Martinez, Andres ;
Nguyen, Allen ;
Young, Judy ;
Barck, Kai H. ;
Carano, Richard A. D. ;
Ferrando, Ron ;
Diehl, Lauri ;
Chatterjea, Devavani ;
Grogan, Jane L. .
NATURE MEDICINE, 2009, 15 (07) :766-U10
[8]   Both Th1 and Th17 are immunopathogenic but differ in other key biological activities [J].
Cox, Catherine A. ;
Shi, Guangpu ;
Yin, Hongen ;
Vistica, Barbara P. ;
Wawrousek, Eric F. ;
Chan, Chi-Chao ;
Gery, Igal .
JOURNAL OF IMMUNOLOGY, 2008, 180 (11) :7414-7422
[9]   Established and novel disease-modifying treatments in multiple sclerosis [J].
Cross, A. H. ;
Naismith, R. T. .
JOURNAL OF INTERNAL MEDICINE, 2014, 275 (04) :350-363
[10]   Interleukin-10 plays a crucial role in suppression of experimental autoimmune encephalomyelitis by Bowman-Birk inhibitor [J].
Dai, Hong ;
Ciric, Bogoljub ;
Zhang, Guang-Xian ;
Rostami, Abdolmohamad .
JOURNAL OF NEUROIMMUNOLOGY, 2012, 245 (1-2) :1-7