Evaluating Mannuronic Acid Effect on Gene Expression Profile of Inflammatory Mediators in Rheumatoid Arthritis Patients

Saiedeh Omidian; Zahra Aghazadeh; Arman Ahmadzadeh; Mona Aslani; Mostafa Hosseini; Simin Abbasi; Abbas Mirshafiey

doi:10.18502/ijaai.v21i1.8612

Saiedeh Omidian Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Zahra Aghazadeh Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Arman Ahmadzadeh Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mona Aslani Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Mostafa Hosseini Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Simin Abbasi Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Abbas Mirshafiey Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i1.8612

Keywords: Interleukin-6; Mannuronic acid; MYD88 deficiency; Toll-like receptor 2; Tumor necrosis

Abstract

Rheumatoid arthritis (RA) is a multisystem disorder. Various studies have shown the important role of inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-22, MYD88,
and toll-like receptor 2 (TLR2) in this disease. In this study, we investigated the anti-inflammatory effects of B-D-Mannuronic acid (M2000), as a new immunosuppressive drug, on the expression of these inflammatory markers in peripheral blood mononuclear cells (PBMCs) of RA patients.

The blood samples of 24 active RA patients and healthy volunteers were used for PBMCs separation. The cells were cultured with LPS (1 µg/mL), low (5 µg/mL), moderate (25 µg/mL), and high (50 µg/mL) doses of M2000 and a single dose of diclofenac (1 µg/mL) to evaluate TNF-α, IL-6, IL-22, MYD88, and TLR2 genes expression by quantitative real-time (qRT-PCR). Cell surface expression and MFI of TLR2 were assessed; using flow cytometry.

Our findings exhibited a significant reduction of TNF-α, IL-6, and MYD88 gene expressions after treatment with three doses of M2000 and an optimum dose of diclofenac. TLR2 gene expression was significantly diminished by moderate and high doses of M2000 and a single dose of diclofenac. Moreoversurface expression of TLR2 was significantly downregulated by moderate and high doses of M2000, while MFI of this was significantly reduced by three doses of M2000.

The results of this research showed that M2000 was able to significantly reduce the gene expression of inflammatory markers TNF-α, IL-6, MYD88, and TLR2 in patients PBMCs. These data revealed a part of the mechanisms of M2000 in the treatment process.