MicroRNA-132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti-inflammation: a new Ahr-based exploration
| Autor: | Hamza, Hanieh, Abdullah, Alzahrani |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Mice Knockout Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Polychlorinated Dibenzodioxins Interleukin-17 Mice Inbred C57BL Interferon-gamma Mice MicroRNAs Gene Expression Regulation Receptors Aryl Hydrocarbon Acetylcholinesterase Animals Humans Molecular Targeted Therapy Transgenes Cells Cultured Cell Proliferation |
| Zdroj: | European journal of immunology. 43(10) |
| ISSN: | 1521-4141 |
| Popis: | MicroRNAs (miRNAs) are a small group of RNAs that are emerging as a new avenue by which autoimmune diseases may be modulated. Accumulating evidence shows that miRNAs are involved in the pathogenesis of MS; however, the interaction of miRNAs with environmentally responsive transcription factors that play prominent roles in MS is unexplored. The activation of aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alleviates inflammation in experimental autoimmune encephalomyelitis (EAE), the best available model of MS. Therefore, we predicted that TCDD could attenuate EAE by inducing miRNA(s) targeting inflammatory mediators. Here, we show that TCDD induces cholinergic anti-inflammation in EAE mice by upregulating acetylcholinesterase-targeting miR-132. The expression of miR-132 was downregulated in CD4⁺ cells and associated with EAE severity, while TCDD treatment attenuated EAE by inducing the miR-132/acetylcholinesterase module. Silencing miR-132 in vivo abolished TCDD-induced cholinergic anti-inflammation and aggravated EAE. Overexpression of miR-132 in encephalitogenic CD4⁺ cells decreased IL-17 and IFN-γ and suppressed T-cell proliferation. In conclusion, our findings identify a new miRNA-based mechanism through which miR-132 mediates TCDD-induced EAE attenuation, suggesting that miR-132 could be a promising therapeutic target for anti-inflammatory treatment of MS. |
| Databáze: | OpenAIRE |
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