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EXPRESSION OF MICRORNAS MIR21, MIR146A, AND MIR155 IN TSC
Conclusion
This study provides supportive evidence of the role of inflammation-related microRNAs in TSC brain, emphasizing the prominent role of astrocytes as source of these microRNA and targets of regulation by IL-1β. In particular, miR146a and miR155 appear to be key players in the regulation of astrocyte-mediated inflammatory response, displaying oppo- site, but interrelated functions. Thus the relationship between activation of the IL-1R/ TLR signaling and the dynamic changes in the ratio between these two miRNAs, involving also noncell autonomous regulation via secreted miRNAs, seem to play a critical role in modulating the immune response in TSC brain. Although IL-1β increased miR146a levels, these levels were not sufficient to reduce IL-1R/TLR signaling. An overexpression of miR146a is required to counteract other coinduced pro-inflammatory miRNAs, such as miR155. Thus, miR146a represents an attractive target for further preclinical studies in neurological disorders, including TSC, associated with a chronic deregulation of the inflammatory response.
Acknowledgements
This work was supported by the National Epilepsy Fund - “Power of the Small”, the Hersenstichting Nederland (NF-13-1;EA), by the Framework Programme FP7/2007-2013 under the project acronym EPISTOP (grant agreement no. 602391; JvS, AI, EA, FJ, KK, SJ, JJ, TS), KIKA (Stichting Kinderen Kankervrij; AP, AE,) and Stichting AMC Foundation (AE, EvV); the Austrian Science Fund (FWF): project no. J3499 (AM). The work of EL was supported by National Science Centre “Sonata” grant no. 2013/11/D/NZ3/01079. JJ is also a recipient of the Foundation for Polish Science “Mistrz” Professorial Subsidy. None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
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