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IL6 Protects MN9D Cells and Midbrain Dopaminergic Neurons from MPP+-Induced Neurodegeneration

NeuroMolecular Medicine volume 14, pages 317–327 (2012)Cite this article

Abstract

The degeneration of midbrain dopaminergic (mDA) neurons is the hallmark of Parkinson’s disease (PD), and several in vivo and in vitro models have been established to resemble the processes occurring during disease progression. One of the most commonly used disease models for PD is the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively kills mDA neurons when applied systemically. In vivo, MPTP intoxication is accompanied by a strong microglia response which is characterised by the release of inflammatory molecules such as tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL6) that are believed to further drive inflammation-mediated degeneration of mDA neurons. Here, we addressed the question whether primary ventral mDA neurons and MN9D cells release cytokines in vitro and how these cytokine profiles change after treatment with MPP+. Our results demonstrate that both culture models show different cytokine profiles under control conditions indicating that comparisons between both models should be made very carefully. Moreover, MN9D cells released high levels of IL6 and IP10/CXCL10, both of which were down regulated after treatment with MPP+. MN9D-derived IL6 seems to be important for MN9D survival since neutralisation of endogenous IL6 resulted in degeneration of MN9D cells. Moreover, recombinant IL6 was able to rescue MN9D cells and primary mDA neuron cultures from MPP+-induced neurotoxicity, underlining the neuroprotective properties of IL6.

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Acknowledgments

The authors thank Susanna Glaser for her excellent technical support.

Conflict of interest

The authors declare that they have no conflict of interests.

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Affiliations

  1. Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Albertstrasse 17, 79104, Freiburg, Germany

    Björn Spittau, Xiaolai Zhou, Ming Ming & Kerstin Krieglstein

  2. Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-University Freiburg, Freiburg, Germany

    Kerstin Krieglstein

  3. Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Ming Ming

  4. Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany

    Xiaolai Zhou

Authors
  1. Björn Spittau
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  2. Xiaolai Zhou
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  3. Ming Ming
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  4. Kerstin Krieglstein
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Correspondence to Björn Spittau.

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Spittau, B., Zhou, X., Ming, M. et al. IL6 Protects MN9D Cells and Midbrain Dopaminergic Neurons from MPP+-Induced Neurodegeneration. Neuromol Med 14, 317–327 (2012). https://doi.org/10.1007/s12017-012-8189-7

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  • DOI: https://doi.org/10.1007/s12017-012-8189-7

Keywords

  • MPP+
  • IL6
  • mDA neurons
  • Neuroprotection
  • Cytokines