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IL-1β Down-Regulates ADAMTS-13 mRNA Expression in Cells of the Central Nervous System

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Abstract

ADAMTS-13 is the Von Willebrand factor (vWF) cleaving protease, responsible for the cleavage and down-regulation of the pro-thrombotic properties of ultra large VWF multimers. It is expressed predominantly by the hepatic stellate cells of the liver, but is also found to be expressed in other tissues, including brain. Reduced ADAMTS-13 is associated with a variety of thrombotic microangiopathies. Since the cellular origin and regulation of ADAMTS-13 expression in the brain is unknown, we aimed to investigate this in four different central nervous system (CNS)-derived cell lines, SHSY–5Y (human neuroblastoma), U373 (human astroglioma), CHME-3 (human foetal microglia) and hCMEC/D3 (adult human brain endothelial cells). All cell lines expressed ADAMTS-13 mRNA constitutively with neuroblastoma cells showing the highest expression. Interleukin (IL)-1β down-regulated ADAMTS-13 mRNA expression in astroglioma cells and microglial cells whereas TNF and IL-6 treatment showed no significant differences in ADAMTS-13 mRNA expression in any cell line tested. ADAMTS-13 protein expression was reduced in a dose-dependent manner only in astroglioma cells following stimulation by IL-1β. The ability of IL-1β to significantly reduce ADAMTS-13 mRNA expression in human microglia and astroglioma cells suggests a role in the haemostasis of the local microenvironment under inflammatory conditions. This is the first report of ADAMTS-13 expression in cells of the CNS; however, its function remains to be determined.

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Acknowledgements

The authors would like to thank Prof. M. Tardieu for providing the microglia, CHME-3, cell line; Prof. P-O. Couraud for providing the human brain endothelial, hCMEC/D3, cell line; and the MRC Brain Bank for the human brain tissue. The Ryder Briggs Trust is acknowledged for funding the project.

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There is no conflict of interest concerning the authors of this study.

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  1. G. Alkistis Frentzou

    Present address: Cardiovascular and Neuronal Remodelling, LIGHT, University of Leeds, Worsley Building, Clarendon Way, Leeds, LS2 9JT, UK

Authors and Affiliations

  1. Biomedical Research Centre, Faculty of Health and Wellbeing, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK

    G. Alkistis Frentzou, Claire Bradford, Gail Haddock, M. Nicola Woodroofe & Alison K. Cross

  2. Department of Neurology, Royal Hallamshire Hospital, Sheffield, S10 2SF, UK

    Kirsty A. Harkness

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  1. G. Alkistis Frentzou
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Correspondence to G. Alkistis Frentzou.

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Frentzou, G.A., Bradford, C., Harkness, K.A. et al. IL-1β Down-Regulates ADAMTS-13 mRNA Expression in Cells of the Central Nervous System. J Mol Neurosci 46, 343–351 (2012). https://doi.org/10.1007/s12031-011-9591-6

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  • DOI: https://doi.org/10.1007/s12031-011-9591-6

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