C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.
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.
Wei
Xing
X
Department of Neurology, Indiana University School of Medicine, 975 West Walnut Street, IB457, Indianapolis, IN 46202, USA.
Chen
Xianming
X
Fontanilla
Christine
C
Zhao
Liming
L
Liang
Zhong
Z
Dodel
Richard
R
Hampel
Hampel
H
Farlow
Martin
M
Du
Yansheng
Y
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
C508584:IL1A protein, human; D053582:Interleukin-1alpha; D012459:Salicylates; D003596:Cytosine; D008148:Lovastatin; D008156:Luciferases; D013941:Thymine