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Influence of β-D-mannuronic Acid, As a New Member of Non-steroidal Anti- Inflammatory Drugs Family, on the Expression Pattern of Chemokines and their Receptors in Rheumatoid Arthritis

Author(s):

Mona Aslani, Arman Ahmadzadeh, Zahra Aghazadeh, Majid Zaki-Dizaji, Laleh Sharifi, Mostafa Hosseini and Abbas Mirshafiey*   Pages 1 - 10 ( 10 )

Abstract:


Background: Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients.

Methods: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry.

Results: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac.

Conclusion: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

Keywords:

Rheumatoid arthritis; β-D-mannuronic acid; M2000; non-steroidal anti-inflammatory drug (NSAID); target molecules (CXCR3, CXCR4, CCR2, CCR5, CCL2/MCP-1)

Affiliation:

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran



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