Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 1 2022 02 06 44 54 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 AND Research Centre for Immunodeficiencies, Children's Medical Centre Hospital, Tehran University of Medical Sciences, Tehran, Iran 2021 03 06 2021 05 22 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 active RA patients and healthy volunteers were used for PBMCsl 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 receptor 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 molecules  TNF-α, IL-6, MYD88, and TLR2 in patients PBMCs. factor-alpha; Rheumatoid arthritis. These data revealed a part of the molecular mechanisms of M2000 in the treatment process. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3142 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3142/1802