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Genetic links between the acute-phase response and arthritis development in rats.

Olofsson, Peter LU ; Nordquist, Niklas; Vingsbo-Lundberg, Carina; Larsson, Anders; Falkenberg, Cecilia LU ; Pettersson, Ulf; Åkerström, Bo LU and Holmdahl, Rikard LU (2002) In Arthritis and Rheumatism 46(1). p.259-268
Abstract
OBJECTIVE: The acute-phase inflammatory response is closely correlated with the development of rheumatoid arthritis, but the pathophysiologic role of its specific components is largely unknown. We investigated the genetic control of the acute-phase protein response in pristane-induced arthritis (PIA), which is a chronic erosive arthritis model in rats. METHODS: Plasma levels of the acute-phase proteins interleukin-6 (IL-6), alpha1-acid glycoprotein (orosomucoid), fibrinogen, and alpha1-inhibitor3 were quantified in 3 strains of rats during the development and progression of disease: DA and LEW.1F, which are susceptible to arthritis, and E3, which is resistant. Genetic linkage analysis was performed on an F2 intercross between E3 and DA to... (More)
OBJECTIVE: The acute-phase inflammatory response is closely correlated with the development of rheumatoid arthritis, but the pathophysiologic role of its specific components is largely unknown. We investigated the genetic control of the acute-phase protein response in pristane-induced arthritis (PIA), which is a chronic erosive arthritis model in rats. METHODS: Plasma levels of the acute-phase proteins interleukin-6 (IL-6), alpha1-acid glycoprotein (orosomucoid), fibrinogen, and alpha1-inhibitor3 were quantified in 3 strains of rats during the development and progression of disease: DA and LEW.1F, which are susceptible to arthritis, and E3, which is resistant. Genetic linkage analysis was performed on an F2 intercross between E3 and DA to determine the genetic control of the acute-phase response in arthritis. Elevated levels of alpha1-acid glycoprotein were associated with acute inflammation, whereas levels of IL-6 were increased during the entire course of the disease. RESULTS: Using these acute-phase markers as quantitative traits in linkage analysis revealed a colocalization of loci controlling the acute-phase response and regions previously shown to control the development of arthritis in chromosomes 10, 12, and 14. In addition, 2 loci that were not associated with arthritis were found to regulate serum levels of the acute-phase protein Apr1 (acute-phase response 1) at the telomeric end of chromosome 12 and Apr2 on chromosome 5. CONCLUSION: The PIA model in rats is a useful tool for understanding some of the pathways leading to chronic erosive arthritis. The analysis of acute-phase proteins in PIA and its application as quantitative traits for studying the genetics of arthritis will promote the understanding of the genetic regulation of the acute-phase response. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Chronic Disease, Non-U.S. Gov't, Terpenes, Support, Inbred Lew, Specific Pathogen-Free Organisms, Rats, Phenotype, Orosomucoid/metabolism, Male, Lod Score, Joints/pathology, Interleukin-6/metabolism, Immunosuppressive Agents, Genotype, Fibrinogen/metabolism, Female, Animal, Breeding, Disease Models, Rheumatoid/chemically induced/*genetics/physiopathology, Arthritis, Acute Disease, Acute-Phase Proteins/*genetics/metabolism
in
Arthritis and Rheumatism
volume
46
issue
1
pages
259 - 268
publisher
John Wiley & Sons
external identifiers
  • pmid:11817600
  • wos:000173428100030
  • scopus:0036161837
ISSN
1529-0131
DOI
10.1002/1529-0131(200201)46:1<259::AID-ART10035>3.0.CO;2-2
language
English
LU publication?
yes
id
ac7ea29e-4b41-4cbe-908e-17f8a192b03d (old id 106326)
date added to LUP
2007-07-18 14:18:19
date last changed
2017-03-26 03:27:35
@article{ac7ea29e-4b41-4cbe-908e-17f8a192b03d,
  abstract     = {OBJECTIVE: The acute-phase inflammatory response is closely correlated with the development of rheumatoid arthritis, but the pathophysiologic role of its specific components is largely unknown. We investigated the genetic control of the acute-phase protein response in pristane-induced arthritis (PIA), which is a chronic erosive arthritis model in rats. METHODS: Plasma levels of the acute-phase proteins interleukin-6 (IL-6), alpha1-acid glycoprotein (orosomucoid), fibrinogen, and alpha1-inhibitor3 were quantified in 3 strains of rats during the development and progression of disease: DA and LEW.1F, which are susceptible to arthritis, and E3, which is resistant. Genetic linkage analysis was performed on an F2 intercross between E3 and DA to determine the genetic control of the acute-phase response in arthritis. Elevated levels of alpha1-acid glycoprotein were associated with acute inflammation, whereas levels of IL-6 were increased during the entire course of the disease. RESULTS: Using these acute-phase markers as quantitative traits in linkage analysis revealed a colocalization of loci controlling the acute-phase response and regions previously shown to control the development of arthritis in chromosomes 10, 12, and 14. In addition, 2 loci that were not associated with arthritis were found to regulate serum levels of the acute-phase protein Apr1 (acute-phase response 1) at the telomeric end of chromosome 12 and Apr2 on chromosome 5. CONCLUSION: The PIA model in rats is a useful tool for understanding some of the pathways leading to chronic erosive arthritis. The analysis of acute-phase proteins in PIA and its application as quantitative traits for studying the genetics of arthritis will promote the understanding of the genetic regulation of the acute-phase response.},
  author       = {Olofsson, Peter and Nordquist, Niklas and Vingsbo-Lundberg, Carina and Larsson, Anders and Falkenberg, Cecilia and Pettersson, Ulf and Åkerström, Bo and Holmdahl, Rikard},
  issn         = {1529-0131},
  keyword      = {Chronic Disease,Non-U.S. Gov't,Terpenes,Support,Inbred Lew,Specific Pathogen-Free Organisms,Rats,Phenotype,Orosomucoid/metabolism,Male,Lod Score,Joints/pathology,Interleukin-6/metabolism,Immunosuppressive Agents,Genotype,Fibrinogen/metabolism,Female,Animal,Breeding,Disease Models,Rheumatoid/chemically induced/*genetics/physiopathology,Arthritis,Acute Disease,Acute-Phase Proteins/*genetics/metabolism},
  language     = {eng},
  number       = {1},
  pages        = {259--268},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {Genetic links between the acute-phase response and arthritis development in rats.},
  url          = {http://dx.doi.org/10.1002/1529-0131(200201)46:1<259::AID-ART10035>3.0.CO;2-2},
  volume       = {46},
  year         = {2002},
}