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Publication year
2008Source
Journal of Leukocyte Biology, 83, 5, (2008), pp. 1295-1299ISSN
Publication type
Article / Letter to editor

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Organization
Internal Medicine
Gastroenterology
Journal title
Journal of Leukocyte Biology
Volume
vol. 83
Issue
iss. 5
Page start
p. 1295
Page end
p. 1299
Subject
IGMD 2: Molecular gastro-enterology and hepatology; N4i 1: Pathogenesis and modulation of inflammation; N4i 2: Invasive mycoses and compromised host; NCMLS 1: Infection and autoimmunity; NCMLS 5: Membrane transport and intracellular motility; UMCN 4.1: Microbial pathogenesis and host defense; UMCN 5.5: Nutrition and HealthAbstract
Amyloid A (AA) amyloidosis is a severe complication of many chronic inflammatory disorders, including the hereditary periodic fever syndromes. However, in one of these periodic fever syndromes, the hyper IgD and periodic fever syndrome, amyloidosis is rare despite vigorous, recurring inflammation. This hereditary syndrome is caused by mutations in the gene coding for mevalonate kinase, an enzyme of the isoprenoid pathway. In this study, we used a cell culture system with human monocytes to show that inhibition of the isoprenoid pathway inhibits amyloidogenesis. Inhibition of the isoprenoid pathway by lovastatin resulted in a dose-dependent reduction of amyloid formed [53% at 10 microM (P=0.01)] compared with mononuclear cells that are exposed only to serum AA. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibited amyloidogenesis. These results implicate that the isoprenoid metabolism could be a potential target for prevention and treatment of AA amyloidosis.
This item appears in the following Collection(s)
- Academic publications [202799]
- Electronic publications [100870]
- Faculty of Medical Sciences [80020]
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