title: Glia maturation factor induces interleukin-33 release from astrocytes: implications for neurodegenerative diseases.
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.
authors: VA Health Care System, Iowa City, IA, USA.
authors: Duraisamy
authors: D
authors: Kempuraj
authors: Mohammad Moshahid
authors: MM
authors: Khan
authors: Ramasamy
authors: R
authors: Thangavel
authors: Zhi
authors: Z
authors: Xiong
authors: Evert
authors: E
authors: Yang
authors: Asgar
authors: A
authors: Zaheer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D020904:Glia Maturation Factor / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020904:Glia Maturation Factor; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha
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