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Fractalkine Induces Hepcidin Expression of BV-2 Microglia and Causes Iron Accumulation in SH-SY5Y Cells

Pandur, Edina, Tamási, Kitti, Pap, Ramóna, Varga, Edit, Miseta, Attila, Sipos, Katalin·2019·Cellular and Molecular Neurobiology
DOI 10.1007/s10571-019-00694-4PMC PMC6711953
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Abstract

Fractalkine (CX3CL1) is a potent inflammatory mediator of the central nervous system, which is expressed by neurons and regulates microglial functions by binding to fractalkine receptor (CX3CR1). It has been demonstrated that neuroinflammation plays an important role in iron accumulation of the brain leading to neuronal cell death. The major regulator of iron homeostasis is the peptide hormone hepcidin. Hepcidin expression is triggered by inflammatory conditions, which may contribute to the neuronal iron accumulation. In the present study, we established a bilaminar co-culture system of differentiated SH-SY5Y cells and BV-2 microglia as a neuronal model to examine the effect of soluble fractalkine on iron homeostasis of microglia and SH-SY5Y cells. We determined the hepcidin expression of fractalkine-treated microglia which showed significant elevation. We examined the relation between increased hepcidin secretion, the known hepcidin regulators and the signalling pathways controlled by fractalkine receptor. Our data revealed that TMPRSS6 and alpha 1-antitrypsin levels decreased due to fractalkine treatment, as well as the activity of NFκB pathway and the tyrosine phosphorylation of STAT5 factor. Moreover, fractalkine-induced hepcidin production of microglia initiated ferroportin internalisation of SH-SY5Y cells, which contributed to iron accumulation of neurons. Our results demonstrate that soluble form of fractalkine regulates hepcidin expression of BV-2 cells through fractalkine-mediated CX3CR1 internalisation. Moreover, fractalkine indirectly contributes to the iron accumulation of SH-SY5Y cells by activating ferroportin internalisation and by triggering the expressions of divalent metal transporter-1, ferritin heavy chain and mitochondrial ferritin.

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Metadata

Authors
Pandur, E., Tamási, K., Pap, R., Varga, E., Miseta, A., & Sipos, K.
ORCID
Pandur, Edina
Venue
Cellular and Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2019-06-06
Volume
39
Issue
7
Pages
985-1001
ISSN
  • 0272-4340
  • 1573-6830
DOI
10.1007/s10571-019-00694-4
PMC
PMC6711953
Cited by
37
References
15
Language
en
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