title: IL6 protects MN9D cells and midbrain dopaminergic neurons from MPP+-induced neurodegeneration.
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.
authors: Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Albertstrasse 17, 79104, Freiburg, Germany. bjoern.spittau@anat.uni-freiburg.de
authors: Björn
authors: B
authors: Spittau
authors: Xiaolai
authors: X
authors: Zhou
authors: Ming
authors: M
authors: Ming
authors: Kerstin
authors: K
authors: Krieglstein
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D009410:Nerve Degeneration / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D016207:Cytokines; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium