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. 2023 May;42(5):1443-1450.
doi: 10.1007/s10067-023-06521-y. Epub 2023 Feb 4.

Investigating the correlation of the NF-κB and FoxP3 gene expression with the plasma levels of pro- and anti-inflammatory cytokines in rheumatoid arthritis patients

Seyed Askar Roghani  1   2   3 , Ramin Lotfi  4 , Bijan Soleymani  3 , Zahra Samimi  1 , Parisa Feizollahi  1 , Shirin Asar  2 , Zahra Abdan  2 , Ali Khorasanizadeh  5 , Mahdi Taghadosi  6
Affiliations

Investigating the correlation of the NF-κB and FoxP3 gene expression with the plasma levels of pro- and anti-inflammatory cytokines in rheumatoid arthritis patients

Seyed Askar Roghani et al. Clin Rheumatol. 2023 May.

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease. Cytokines regulate a wide range of inflammatory processes involved in RA pathogenesis. Anti-inflammatory cytokines (i.e., TGF-β and lL-10) and pro-inflammatory cytokines, like IL-6, were found to be potentially implicated in RA pathogenesis. Besides, NF-κB and FoxP3 are critical transcription factors regulating the inflammatory events occurring in RA patients. This study intends to assess the plasma levels of IL-6, IL-10, and TGF-β1 cytokines, as well as the expression of NF-κB and FoxP3 genes in RA patients, compared to the healthy controls.

Methods: Peripheral blood was collected from 50 RA patients (25 new case and 25 under-treatment) and 25 age- and gender-matched healthy subjects. The disease activity was determined using the DAS-28 and ESR criteria. Also, plasma levels of TGF-β1, lL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) technique, and the gene expression of NF-κB and FoxP3 was evaluated using the real-time PCR method.

Results: Our results showed a significant up-regulation of Rel-A and NF-κB1, and also a down-regulation of FoxP3 gene expression in under-treatment RA patients compared to the controls (P=0.031, P=0.014, and P=0.011, respectively). Moreover, there was a significant reduction of Rel-A and FoxP3 in the under-treatment RA patients compared to new case RA patients (P=0.005 and P=0.015, respectively). Also, plasma levels of TGF-β1 were significantly increased in both the new case and under-treatment RA patients relative to controls (P<0.001).

Conclusion: In conclusion, classical NF-κB (P65/P50) and FoxP3 may have significant pro- and anti-inflammatory roles in RA pathogenesis, respectively. Key Point • NF-κB (P65/P50) has a contribution to the early phase of RA.

Keywords: FoxP3; NF-κB; Regulatory T cell; Rheumatoid Arthritis; TGF-β1.

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