Abstract
Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The identification of cell surface molecules that mediate the prion protein (PrP) synthetic peptide interaction with microglia is of great significance as it represents potential target molecules to modulate the events leading to the pathophysiology of prion diseases. Here, we carried out in vitro experiments to investigate the involvement of α5β1 integrin in neurotoxic prion peptide PrP106–126-induced activation of BV2 microglia. The results showed that the exposure to PrP106–126 upregulated the mRNA expression of proinflammatory factors (IL-1 β, IL-6, and iNOS) and NALP3 inflammasome components (NALP3 and ASC), increased the release of iNOS and its product nitric oxide, and stimulated NF-κB activation. Blockade of α5β1 integrin with monoclonal antibody BMC5 prior to PrP106–126 treatment abrogated the upregulation of the mRNA expression of IL-1 β, IL-6, iNOS, and ASC, but had no effect on the mRNA expression of NALP3, blocked the release of iNOS and nitric oxide, and inhibited NF-κB activation. These results suggest that α5β1 integrin is involved in the PrP106–126-induced microglial activation through the participation in the activation of NF-κB and NALP3/ASC inflammasome. Our study unveils a previously unidentified role of α5β1 integrin as an intermediate signaling molecule in neurotoxic prion peptides–microglia interactions and identifies a potential molecular target for the modulation of prion-induced microglial activation.
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Acknowledgments
This work was supported by the Natural Science Foundation of China (project nos. 31001048, 31172293, and 30972164), Specialized Research Fund for the Doctoral Program of Higher Education (project no. 20100008120002), and the Program for Cheung Kong Scholars and Innovative Research Team in the University of China (no. IRT0866).
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We declare that no competing interests exist and that those who provided funds had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Jiaxin Chang, Lifeng Yang, and Mohammed Kouadir contributed equally to this work.
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Chang, J., Yang, L., Kouadir, M. et al. Antibody-Mediated Inhibition of Integrin α5β1 Blocks Neurotoxic Prion Peptide PrP106–126-Induced Activation of BV2 Microglia. J Mol Neurosci 48, 248–252 (2012). https://doi.org/10.1007/s12031-012-9821-6
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DOI: https://doi.org/10.1007/s12031-012-9821-6