Role of TRIF Small Interference RNA (siRNA) in Chronic Experimental Allergic Encephalomyelitis (EAE).
BACKGROUND
Multiple sclerosis (MS) is an autoimmune disease causing multifocal demyelination and axonal injuries in the central nervous system (CNS). Toll-interleukin-1 receptor (TIR)-domain containing adaptor protein-inducing interferon beta (TRIF) is an important adaptor protein for Toll-like receptors (TLRs) and can modulate the immune response via regulating cytokine secretion. This study investigated the potential function of TRIF in MS mice via small interference RNA (siRNA).


METHODS
Isolated mouse lymphocytes were processed using TRIF siRNA, followed by RT-PCR assay to quantify TRIF expression level. An experimental allergic encephalomyelitis (EAE) model was prepared in C57BL/6 mice immunized with MOG 35-55. TRIF siRNA or controlled siRNA were intravenously applied to evaluate the neurological function of animals. Serum levels of IFN-γ and IL-2 were observed.


RESULTS
Specific siRNA effectively decreased the TRIF expression in mouse dendritic cells and this siRNA improved the EAE severity and neurological scores. Further assays showed that both IFN-γ and IL-2 levels in the siRNA treatment group were significantly lower than in controls.


CONCLUSIONS
The expression of TRIF can be down-regulated by siRNA, thereby alleviating the severity of EAE via its inhibition of interleukin and cytokine release. This may provide new insights for future treatment of MS.
Department of Gerontological Neurology, Heilongjiang Hospital, Harbin, Heilongjiang, China (mainland).
Xichun
X
Wang
Department of Cardiology, Heilongjiang Hospital, Harbin, Heilongjiang, China (mainland).
Xiufeng
X
Zheng
Department of Cardiology, Heilongjiang Hospital, Harbin, Heilongjiang, China (mainland).
Chong
C
Ma
Department of Gerontological Neurology, Heilongjiang Hospital, Harbin, Heilongjiang, China (mainland).
Libo
L
Zhao
D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000276:immunology; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*
D033942:Adaptor Proteins, Vesicular Transport; D007371:Interferon-gamma; D007376:Interleukin-2; D034741:RNA, Small Interfering; C476286:Ticam1 protein, mouse