Genetic links between the acute-phase response and arthritis development in rats.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/106326
- author
- Olofsson, Peter LU ; Nordquist, Niklas ; Vingsbo-Lundberg, Carina ; Larsson, Anders ; Falkenberg, Cecilia LU ; Pettersson, Ulf ; Åkerström, Bo LU and Holmdahl, Rikard LU
- organization
- publishing date
- 2002
- 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 Inc.
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019), Division of Infection Medicine (BMC) (013024020), Department of Experimental Medical Science (013210000)
- id
- ac7ea29e-4b41-4cbe-908e-17f8a192b03d (old id 106326)
- date added to LUP
- 2016-04-01 11:42:25
- date last changed
- 2022-02-03 03:18:14
@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}}, 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}}, language = {{eng}}, number = {{1}}, pages = {{259--268}}, publisher = {{John Wiley & Sons Inc.}}, 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}}, doi = {{10.1002/1529-0131(200201)46:1<259::AID-ART10035>3.0.CO;2-2}}, volume = {{46}}, year = {{2002}}, }