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Inhibition of CDK9 ...
Inhibition of CDK9 as a therapeutic strategy for inflammatory arthritis
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Hellvard, Annelie (författare)
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Zeitlmann, L. (författare)
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Heiser, U. (författare)
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Kehlen, A. (författare)
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Niestroj, A. (författare)
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Demuth, H. U. (författare)
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Koziel, J. (författare)
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Delaleu, N. (författare)
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Potempa, J. (författare)
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- Mydel, Piotr, 1974 (författare)
- 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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(creator_code:org_t)
- 2016-08-11
- 2016
- Engelska.
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
- Relaterad länk:
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https://gup.ub.gu.se... (primary) (free)
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Rheumatoid arthritis is characterised by synovial inflammation and proliferation of fibroblast-like synoviocytes. The induction of apoptosis has long been proposed as a target for proliferative autoimmune diseases, and has further been shown to act as a successful treatment of experimental models of arthritis, such as collagen-induced arthritis. Here we examined the effects of specific oral small-molecule inhibitors of the transcription regulating cyclin-dependent kinase 9 on the development and progression of collagen-induced arthritis. DBA/1 mice were immunised with bovine collagen type II and treated orally with specific CDK9 inhibitors. The effects of CDK9 inhibition on RNA levels and protein expression, apoptosis induction, caspase activation and lymphocyte phenotype were further analysed. Mice showed a significant delay in disease onset and a reduction in disease severity following treatment with CDK9 inhibitors. Inhibiting CDK9 activity in peripheral blood mononuclear cells resulted in the loss of Mcl-1 expression at both the protein and RNA levels, along with a subsequent increase in apoptosis. CDK9 specific inhibitors may be a potential alternative treatment not only of cancer, but also for autoimmune-and inflammatory diseases. Taken together, these results show that transient inhibition of CDK9 induces apoptosis in leukocyte subsets and modulates the immune response.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- COLLAGEN-INDUCED ARTHRITIS
- RNA-POLYMERASE-II
- DEPENDENT KINASE
- INHIBITORS
- REGULATORY T-CELLS
- RHEUMATOID-ARTHRITIS
- SYNOVIAL-FLUID
- ADHESION MOLECULE-1
- PERIPHERAL-BLOOD
- CANCER-CELLS
- IN-VIVO
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Hellvard, Anneli ...
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Zeitlmann, L.
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Heiser, U.
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Kehlen, A.
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Niestroj, A.
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Demuth, H. U.
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visa fler...
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Koziel, J.
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Delaleu, N.
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Potempa, J.
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Mydel, Piotr, 19 ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
- Artiklar i publikationen
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Scientific Repor ...
- Av lärosätet
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Göteborgs universitet