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TNF production in m...
TNF production in macrophages is genetically determined and regulates inflammatory disease in rats.
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- Gillett, Alan (author)
- Karolinska Institutet
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- Marta, Monica (author)
- Karolinska Institutet
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- Jin, Tao, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Tuncel, Jonatan (author)
- Karolinska Institutet
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Leclerc, Patrick (author)
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Nohra, Rita (author)
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- Lange, Stefan, 1948 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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- Olsson, Tomas (author)
- Karolinska Institutet
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- Harris, Robert A (author)
- Karolinska Institutet
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Jagodic, Maja (author)
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(creator_code:org_t)
- 2010-07-01
- 2010
- English.
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 185:1, s. 442-50
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Abstract
Subject headings
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- Dysregulation of TNF is an important pathophysiological phenotype for many diseases. Recently, certain genetically regulated loci have been identified to regulate several inflammatory diseases. We hypothesized that a region on rat chromosome 4 known to regulate experimental autoimmune encephalomyelitis, experimental arthritis and experimental autoimmune neuritis harbors a gene regulating central inflammatory molecules, such as TNF. We therefore mapped TNF production using linkage analysis in the 12th generation of an advanced intercross line between DA and PVG.AV1 rats, which differ in susceptibility to several inflammatory conditions. A single TNF-regulating quantitative trait locus with a logarithm of odds score of 6.2 was identified and its biological effect was confirmed in a congenic rat strain. The profound TNF regulation mapped in congenic strains to the macrophage population. Several TLR signaling cascades led to the same reduced proinflammatory phenotype in congenic macrophages, indicating control of a convergence point for innate inflammatory activity. The decreased TNF potential and reduced proinflammatory macrophage phenotype in congenic rats was also associated with reduced clinical severity in experimental autoimmune encephalomyelitis, pristane-induced arthritis and sepsis experimental models. Determination of genes and mechanisms involved in this genetically determined TNF regulation will be valuable in understanding disease pathogenesis and aid treatment development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- TNF
- macrophage
- inflammatory disease
- rats
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Gillett, Alan
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Marta, Monica
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Jin, Tao, 1973
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Tuncel, Jonatan
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Leclerc, Patrick
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Nohra, Rita
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show more...
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Lange, Stefan, 1 ...
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Holmdahl, Rikard
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Olsson, Tomas
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Harris, Robert A
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Jagodic, Maja
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
- Articles in the publication
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Journal of immun ...
- By the university
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University of Gothenburg
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Karolinska Institutet