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Glia Maturation Factor Induces Interleukin-33 Release from Astrocytes: Implications for Neurodegenerative Diseases

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Abstract

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Multiple sclerosis (MS) involve activation of glial cells and release of inflammatory mediators leading to death of neurons. Glia maturation factor (GMF) is up-regulated in the central nervous system (CNS) in these neurodegenerative diseases. Interleukin-33 (IL-33) is highly expressed constitutively in the CNS. We have treated mouse astrocytes, mixed culture with glial cells and neurons, and only neurons with GMF and/or IL-33 in vitro. Both GMF and IL-33-induced chemokine (C-C motif) ligand 2 (CCL2) release in a dose and time-dependent manner. We report that GMF induced IL-33 release, and that IL-33 augments GMF-induced tumor necrosis factor-alpha (TNF-α) release from mouse astrocytes. IL-33 induces CCL2, TNF-α and nitric oxide release through phosphorylation of ERK in mouse astrocytes. Incubation of mixed culture containing glial cells and neurons or only neuronal culture with IL-33 reduced the number of neurons positive for microtubule-associated protein 2. In conclusion, IL-33 augments GMF-mediated neuroinflammation and may provide a new drug target for neurodegenerative and autoimmune diseases.

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Acknowledgments

This work was supported by the Department of Veterans Affairs Merit Review award (to A.Z.) and by the National Institute of Neurological Disorders and Stroke grants NS073670 (to A.Z.)

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Authors and Affiliations

  1. VA Health Care System, Iowa City, IA, USA

    Duraisamy Kempuraj, Ramasamy Thangavel, Evert Yang & Asgar Zaheer

  2. Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA

    Duraisamy Kempuraj, Mohammad Moshahid Khan, Ramasamy Thangavel, Zhi Xiong & Asgar Zaheer

Authors
  1. Duraisamy Kempuraj
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  2. Mohammad Moshahid Khan
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  3. Ramasamy Thangavel
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  4. Zhi Xiong
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  5. Evert Yang
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  6. Asgar Zaheer
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Corresponding author

Correspondence to Asgar Zaheer.

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Kempuraj, D., Khan, M.M., Thangavel, R. et al. Glia Maturation Factor Induces Interleukin-33 Release from Astrocytes: Implications for Neurodegenerative Diseases. J Neuroimmune Pharmacol 8, 643–650 (2013). https://doi.org/10.1007/s11481-013-9439-7

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  • DOI: https://doi.org/10.1007/s11481-013-9439-7

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