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Efficacy of DMARDs Therapy on the Disease Activity and Gene Expression Levels of FoxO1, FoxO3, Runx1, and Runx3 in
Seyed Askar Roghani1, Ramin Lotfi2,3, Shirin Assar4
1Department of Anatomical Sciences, Faculty of Medical Sciences Tarbiat Modares University Tehran Iran.
Background And Aims:
Forkhead box O (FoxO) transcription factors exert crucial roles in immune responses. Besides, the Runt-related transcription factor (Runx) family plays a pivotal role in the development and homeostasis of cartilage and bone. This study assessed the plasma concentrations of the pro-inflammatory interleukin-6 (IL-6) cytokine and the anti-inflammatory cytokine interleukin-10 (IL-10), as well as the gene expression levels of FoxO1, FoxO3, Runx1, and Runx3, in the peripheral blood sample of the early rheumatoid arthritis (RA) patients treated with conventional disease-modifying antirheumatic drugs (DMARDs) for 6 months relative to normal subjects.
Methods:
This study examined 30 early DMARDs-naïve RA patients (before and after treatment) and 30 age- and gender-matched normal individuals. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression amounts of FoxO1, FoxO3, Runx1, and Runx3 were determined using real-time PCR.
Results:
The plasma IL-6 concentrations increased significantly in pre- and posttreatment RA patients compared with controls (p < 0.001). Moreover, the gene expression of FoxO1 and FoxO3 was enhanced considerably in RA patients (both before and after treatment), compared to controls (p < 0.001 for FoxO1 and p = 0.02 and p = 0.01 for FoxO3, respectively). Runx1 gene expression increased dramatically in pre- and posttreatment RA patients compared with the controls (p < 0.001). Runx3 gene expression was meaningfully enhanced in pretreatment RA patients than in normal controls (p < 0.001). Also, DMARDs treatment strikingly reduced Runx3 gene expression levels compared to pretreatment levels (p < 0.001).
Conclusion:
DMARDs treatment dramatically diminishes Runx3 gene expression, thereby lowering disease activity and inflammatory markers in the early RA patients.
Insights
Disease-modifying antirheumatic drugs (DMARDs) treatment significantly reduced Runx3 gene expression in early rheumatoid arthritis (RA) patients. This suggests DMARDs may lower RA disease activity and inflammation by modulating Runx3.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Forkhead box O (FoxO) transcription factors are key in immune responses.
- Runt-related transcription factor (Runx) family is vital for cartilage and bone homeostasis.
- Understanding these factors in rheumatoid arthritis (RA) is crucial.
Purpose of the Study:
- To assess plasma cytokine levels (IL-6, IL-10) and gene expression of FoxO1, FoxO3, Runx1, and Runx3.
- To compare these markers in early RA patients before and after disease-modifying antirheumatic drugs (DMARDs) treatment versus healthy controls.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) for IL-6 and IL-10 plasma levels.
- Real-time PCR for FoxO1, FoxO3, Runx1, and Runx3 mRNA expression.
- Study included 30 early RA patients (pre- and post-treatment) and 30 controls.
Main Results:
- Elevated plasma IL-6 in RA patients (pre- and post-treatment) compared to controls.
- Increased gene expression of FoxO1 and FoxO3 in RA patients (pre- and post-treatment).
- Significantly higher Runx1 expression in RA patients; Runx3 expression was elevated pre-treatment but reduced post-DMARDs therapy.
Conclusions:
- DMARDs treatment significantly downregulates Runx3 gene expression in early RA.
- This reduction in Runx3 may contribute to decreased disease activity and inflammation in RA patients.
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