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- W4313356477 abstract "Abstract Huntington’s disease (HD) is an inherited neurodegenerative disease with impairment of motor and cognitive functions. Studies in HD gene carriers expressing mutant huntingtin protein (mHTT) demonstrated altered immune response indicating that cytokines may have a significant role in disease development. We utilized the novel transgenic HD model bearing N-fragment of human mHTT in minipig (Baxa M et al., J Huntington’s Dis. 2013, 2:47–68), to investigate central nervous and peripheral cytokine levels. Using Luminex® xMAP™ multiplexing technology and Thermo Fisher Scientific Inc., Swine Cytokine Magnetic 7-plex Panel (Invitrogen™ LSC0001M), the biological fluids were interrogated to identify cytokine alterations related to HD progression. The modelling of interaction networks between such cytokines and HTT facilitated study of intracellular signaling pathways associated with immune response dysregulation. The most pronounced change was the decline of IFNα in cerebrospinal fluid and secretome of microglial cells (MG). In addition, IL-10 was also lower in the same biological fluids. Elevated levels of pro-inflammatory IL-1 and IL-8 were secreted by MG whilst IL-8 was also increased in serum of transgenic minipigs. The high proportion of mHTT in MG may have a causative impact on cytokine production. A novel role for CREB-binding protein in HD pathogenesis was highlighted. These findings underlined the roles of IFNα, IL-10, IL-1 and IL-8 in central nervous system inflammation and immune response imbalance in HD progression warrants further investigation into their usefulness in human patients. Acknowledgement We thank CHDI, MESY Projects EXAM; CZ.1.05/2.1.00/03.0124, LO1609 and Thermo Fisher Scientific for expertise." @default.
- W4313356477 created "2023-01-06" @default.
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- W4313356477 date "2016-05-01" @default.
- W4313356477 modified "2023-10-09" @default.
- W4313356477 title "Emerging roles of IFNα, IL-10, IL-1 and IL-8 in central nervous inflammation and immune response imbalance in transgenic porcine model of neurodegenerative Huntington’s disease" @default.
- W4313356477 doi "https://doi.org/10.4049/jimmunol.196.supp.51.10" @default.
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