title: Alzheimer's disease: evidence for the expression of interleukin-33 and its receptor ST2 in the brain.
abstract: Inflammatory responses are increasingly implicated in the pathogenesis of neurodegenerative diseases such as in Alzheimer's disease (AD). Interleukin-33 (IL-33), a member of IL-1 family, is constitutively expressed in the central nervous system and thought to be an important mediator of glial cell response to neuropathological lesions. Proinflammatory molecules are highly expressed at the vicinity of amyloid plaques (APs) and neurofibrillary tangles (NFTs), the hallmarks of AD pathology. We have investigated the expression of IL-33 and ST2 in relation to APs and NFTs in human AD and non-AD control brains by immunohistochemistry. Sections from the entorhinal cortex, where APs and NFTs appear in early stages of AD, were used for immunohistochemistry. Mouse primary astrocytes were cultured and incubated with amyloid-β1-42 (Aβ1-42), component of plaque for 72 h and analyzed for the expression of IL-33 by flow cytometry. We found strong expression of IL-33 and ST2 in the vicinity of Aβ and AT8 labelled APs and NFTs respectively, and in the glial cells in AD brains when compared to non-AD control brains. IL-33 and ST2 positive cells were also significantly increased in AD brains when compared to non-AD brains. Flow cytometric analysis revealed incubation of mouse astrocytes with Aβ1-42 increased astrocytic IL-33 expression in vitro. These results suggest that IL-33, an alamin cytokine, may induce inflammatory molecule release from the glial cells and may play an important role in the pathogenesis of AD.
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Veterans Affairs Health Care System, Iowa City, IA, USA Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Thangavel
authors.affiliation: Veterans Affairs Health Care System, Iowa City, IA, USA Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Kempuraj
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Evert
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Smita
authors.initials: S
authors.lastname: Zaheer
authors.affiliation: Veterans Affairs Health Care System, Iowa City, IA, USA Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Asgar
authors.initials: A
authors.lastname: Zaheer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016900:Neurofilament Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; IL-33; ST2; amyloid plaques; glia maturation factor; neurofibrillary tangles