title: C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.
abstract: Recently, association of an interleukin-1A promoter polymorphism (-889, thymine/thymine (T/T)) with Alzheimer's disease was reported, suggesting that this cytokine may play an important role in disease development. To understand the mechanism underlying the interleukin-1A promoter's role in Alzheimer's disease, a study comparing promoter function of an interleukin-1A polymorphism was performed in the SVG astroglia cell line. The effects of thymine and cytosine on transcriptional activity of the interleukin-1A promoter were analyzed by testing luciferase-reporter activity in transfected SVG cells. Our results demonstrate that cytosine/thymine conversion increases activity of the interleukin-1A promoter in SVG cells. Both sodium salicylate and lovastatin are able to block induced promoter activities in astroglial cells. Induced promoter activity by the polymorphism (T/T) may result in the upregulation of interleukin-1alpha protein and "cytokine cycle" amplification, which may promote disease development.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, 975 West Walnut Street, IB457, Indianapolis, IN 46202, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Xianming
authors.initials: X
authors.lastname: Chen
authors.forename: Christine
authors.initials: C
authors.lastname: Fontanilla
authors.forename: Liming
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liang
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.forename: Hampel
authors.initials: H
authors.lastname: Hampel
authors.forename: Martin
authors.initials: M
authors.lastname: Farlow
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D003596:Cytosine; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D008148:Lovastatin / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D010957:Plasmids; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D012459:Salicylates / Q000494:pharmacology; D013941:Thymine; D014162:Transfection
chemical_list: C508584:IL1A protein, human; D053582:Interleukin-1alpha; D012459:Salicylates; D003596:Cytosine; D008148:Lovastatin; D008156:Luciferases; D013941:Thymine