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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

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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.

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Abbreviations

RA:

Rheumatoid arthritis

FoxP3:

Forkhead box P3

TGF-β:

Transforming growth factor-β

IL-6:

Interleukin 6

Treg cell:

Regulatory T cell

NFAT:

Nuclear factor of activated T cells

NF-κB:

Nuclear factor-κB

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Acknowledgements

The authors would like to thank all subjects who eagerly participated in this study. This work was accomplished in partial fulfillment of the requirements for the M.Sc. thesis of Seyed Askar Roghani, in the School of Medicine, Kermanshah University of Medical Sciences (KUMS), Kermanshah, Iran.

Funding

This study was financially supported by the deputy of research and technology of the Kermanshah University of Medical Sciences, Kermanshah, Iran [Grant Number: 95709].

Author information

Authors and Affiliations

  1. Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Seyed Askar Roghani, Zahra Samimi, Parisa Feizollahi & Mahdi Taghadosi

  2. Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Seyed Askar Roghani, Shirin Asar & Zahra Abdan

  3. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Seyed Askar Roghani & Bijan Soleymani

  4. Clinical Research Development Center, Tohid Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Ramin Lotfi

  5. Student Research Committee, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Ali Khorasanizadeh

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  1. Seyed Askar Roghani
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All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

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Correspondence to Mahdi Taghadosi.

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Roghani, S.A., Lotfi, R., Soleymani, B. et al. 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. Clin Rheumatol 42, 1443–1450 (2023). https://doi.org/10.1007/s10067-023-06521-y

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