Abstract
Gene silencing with siRNAs is important as a therapeutic tool in autoimmune diseases. In this study, we administered siRNAs specific for cytokines that may be involved in pathogenesis of experimental autoimmune encephalomyelitis (EAE). siRNA specific for IL-23p19 (siRNA-IL-23) suppressed EAE almost completely, whereas siRNA-IL-17A did not modulate the clinical course. Flow cytometric analysis revealed that siRNA-IL-23 significantly reduced the proportion of both IFN-γ(+)IL-17(-) Th1 and IFN-γ(-)IL-17(+) Th17 cells in the spinal cord. Consistent with this finding, siRNA-IL-23 treatment downregulated IL-12, IL-17 and IL-23 mRNAs. These findings indicate that IL-23, but not IL-17, play an important role in the development of EAE.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Cytokines / genetics
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Cytokines / metabolism
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Disease Models, Animal
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Drug Delivery Systems
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Encephalomyelitis, Autoimmune, Experimental / therapy*
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Flow Cytometry
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Freund's Adjuvant / adverse effects
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Interleukin-12 / genetics
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Interleukin-12 / metabolism*
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Interleukin-17 / genetics
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Interleukin-17 / metabolism*
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Myelin Basic Protein / immunology
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Myelin Basic Protein / metabolism
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / therapeutic use*
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Rats
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Rats, Inbred Lew
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Severity of Illness Index
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Spinal Cord / drug effects
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Spinal Cord / metabolism
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Statistics, Nonparametric
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Th1 Cells / drug effects
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Th1 Cells / metabolism
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Th17 Cells / drug effects
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Th17 Cells / metabolism
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Time Factors
Substances
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Cytokines
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Interleukin-17
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Myelin Basic Protein
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RNA, Messenger
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RNA, Small Interfering
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Interleukin-12
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Freund's Adjuvant