WFRF:(Ekwall Anna Karin H)
Sökning: WFRF:(Ekwall Anna Karin H) > (2015-2019) > Methotrexate inhibi...
- Bergström, BeatriceGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Rheumatology and Inflammation Research (författare)
Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
- 2018-03-20
- Springer Science and Business Media LLC,2018
Nummerbeteckningar
- LIBRIS-ID:oai:gup.ub.gu.se/266151
- https://gup.ub.gu.se/publication/266151URI
- https://doi.org/10.1186/s13075-018-1554-7DOI
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- Språk:engelska
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- SwePubSwePub
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- Background: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro. Methods: Primary FLS from patients with RA or osteoarthritis were stimulated with the mitogen platelet-derived growth factor (PDGF) and the cytokine interleukin-1β (IL-1β) in the presence or absence of MTX. Cells were then subjected to qPCR for gene expression and cell cycle analysis by flow cytometry. Results: Stimulation with PDGF and IL-1β increased the percentage of FLS in the G2/M phase and shifted the cell morphology to a dendritic shape. These effects were inhibited by MTX. Furthermore, PDGF + IL-1β reduced LBH mRNA expression. However, MTX treatment yielded significantly higher transcript levels of LBH, and of CDKN1A (p21) and TP53 (p53), compared to untreated samples upon mitogen stimulation. The expression of DNA methyltransferase-1 (DNMT1) was also higher in the presence of MTX and there was strong correlation between DNMT1 and LBH expression. Conclusions: Therapeutic concentrations of MTX abolish the effects of PDGF and IL-1β on tumor suppressor expression and inhibit mitogen-promoted FLS proliferation. These data demonstrate novel and important effects of MTX on pathogenic effector cells in the joint, which might involve epigenetic mechanisms. © 2018 The Author(s).
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reumatologi och inflammation hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Rheumatology and Autoimmunity hsv//eng
- Cell cycle
- Fibroblast-like synoviocytes
- Interleukin-1beta
- Methotrexate
- Platelet-derived growth factor
- Rheumatoid arthritis
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Carlsten, Hans,1954Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xcahan (författare)
- Ekwall, Anna-Karin HGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xhannp (författare)
- Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Arthritis Research and Therapy: Springer Science and Business Media LLC20:491478-63541478-6362
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