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

• Published in: Clinical rheumatology Vol. 42; no. 5; pp. 1443 - 1450
• Main Authors: Roghani, Seyed Askar, Lotfi, Ramin, Soleymani, Bijan, Samimi, Zahra, Feizollahi, Parisa, Asar, Shirin, Abdan, Zahra, Khorasanizadeh, Ali, Taghadosi, Mahdi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.05.2023; Springer Nature B.V
• Subjects: Anti-Inflammatory Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; Cytokines; Enzyme-linked immunosorbent assay; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Forkhead Transcription Factors - therapeutic use; Foxp3 protein; Gene Expression; Humans; Interleukin 10; Interleukin 6; Interleukin-6 - genetics; Medicine; Medicine & Public Health; NF-kappa B - genetics; NF-kappa B - metabolism; NF-kappa B - therapeutic use; NF-κB protein; Original Article; Pathogenesis; Peripheral blood; Plasma; Plasma levels; Rheumatoid arthritis; Rheumatology; Transcription factors; Transforming Growth Factor beta1 - genetics; Transforming growth factor-b; Transforming growth factor-b1; NF-κB; TGF-β1; Rheumatoid Arthritis; FoxP3; Regulatory T cell
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-023-06521-y

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 .