Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Influence of Β-D-Mannuronic Acid, As a New Member of Non-Steroidal An-Ti-Inflammatory Drugs Family, on the Expression Pattern of Chemokines and Their Receptors in Rheumatoid Arthritis Publisher Pubmed



Aslani M1 ; Ahmadzadeh A2 ; Aghazadeh Z1 ; Zakidizaji M3 ; Sharifi L4 ; Hosseini M5 ; Mirshafiey A1, 3
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Source: Current Drug Discovery Technologies Published:2021


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 was down-regulated significantly followed by the treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after the treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by the treatment of these cells with a high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by the treatment of these cells with a 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. © 2021 Bentham Science Publishers.
Related Docs
View other Related Docs
1. The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Administration of Drug Mannuronic Acid in Rheumatoid Arthritis Patients, Recent Patents on Inflammation and Allergy Drug Discovery (2020)
2. Β-D-Mannuronic Acid (M2000) As a Landmark in Pharmacology, Current Drug Discovery Technologies (2021)
3. The Role of Β-D-Mannuronic Acid, As a New Non-Steroidal Anti-Inflammatory Drug on Expression of Mir-146A, Irak1, Traf6, Nf-Κb and Pro-Inflammatory Cytokines Following a Clinical Trial in Rheumatoid Arthritis Patients, Immunopharmacology and Immunotoxicology (2020)
4. International Multicenter Randomized, Placebo-Controlled Phase Iii Clinical Trial of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients, Inflammopharmacology (2019)
5. Evaluating Mannuronic Acid Effect on Gene Expression Profile of Inflammatory Mediators in Rheumatoid Arthritis Patients, Iranian Journal of Allergy# Asthma and Immunology (2022)
6. The Effects of Mannuronic Acid on Il-1Β, Il-17A, Stat1, and Stat3 Gene Expressions and Tlr2 and Tlr4 Molecules in Multiple Sclerosis, Journal of Clinical Pharmacology (2022)
7. A Randomized, Controlled, Phase Ii Clinical Trial of Β-D-Mannuronic Acid (M2000) in Pre-Surgical Breast Cancer Patients at Early Stage (T1-T2), Clinical and Experimental Pharmacology and Physiology (2019)
8. Anti-Diabetic Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property on Insulin Production, Blood Glucose, and Inflammatory Markers in the Experimental Diabetes Model, Archives of Physiology and Biochemistry (2019)
Experts (# of related papers)
View all Related Experts
Mahdi Mahmoudi (9)
Ahmad Reza Jamshidi (8)
Other Related Docs
9. Mannuronic Acid in Low-Risk and Intermediate-1-Risk Myelodysplastic Syndromes, Journal of Clinical Pharmacology (2020)
10. Immunopharmacological Effect of Β-D-Mannuronic Acid (M2000), As a New Immunosuppressive Drug, on Gene Expression of Mir-155 and Its Target Molecules (Socs1, Ship1) in a Clinical Trial on Rheumatoid Arthritis Patients, Drug Development Research (2020)
11. Efficacy of Β-D-Mannuronic Acid [M2000] on the Pro-Apoptotic Process and Inflammatory-Related Molecules Nfҡb, Il-8 and Cd49d Using Healthy Donor Pbmc, Current Drug Discovery Technologies (2020)
12. Β-D-Mannuronic Acid (M2000) and Inflammatory Cytokines in Covid-19; an in Vitro Study, Iranian Journal of Allergy# Asthma and Immunology (2022)
13. Cardioprotective Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid on Gene Expression of Oxldl Scavenger Receptors in the Experimental Diabetic Model, Immunopharmacology and Immunotoxicology (2018)
14. A Controlled, Randomized Phase Ii Clinical Trial for Efficacy and Safety Evaluation of Mannuronic Acid in Secondary Progressive Form of Multiple Sclerosis, International Journal of Neuroscience (2022)
15. A Phase I/Ii Randomized, Controlled, Clinical Trial for Assessment of the Efficacy and Safety of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients, Inflammopharmacology (2018)
16. The Inhibitory Role of M2000 (Β-D-Mannuronic Acid) on Expression of Toll-Like Receptor 2 and 4 in Ht29 Cell Line, Recent Patents on Inflammation and Allergy Drug Discovery (2019)
17. The Anti-Tumoral Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid on Treg Cells Frequency and Mmp-2, Mmp-9, Ccl22 and Tgfβ1 Gene Expression in Pre-Surgical Breast Cancer Patients, Iranian Journal of Allergy# Asthma and Immunology (2019)
18. Dysregulated Mirnas Network in the Critical Covid-19: An Important Clue for Uncontrolled Immunothrombosis/Thromboinflammation, International Immunopharmacology (2022)
19. An in Vitro Assessment for Evaluating the Efficiency of Β-D-Mannuronic Acid (M2000) in Myelodysplastic Syndrome, Journal of Cellular Physiology (2019)
20. Anti-Tumor Effect of M2000 (Β-D-Mannuronic Acid) on the Expression of Inflammatory Molecules in the Prostate Cancer Cell, Immunopharmacology and Immunotoxicology (2021)
21. Evaluation of the Effect of Mannuronic Acid As a Novel Nsaid With Immunosuppressive Properties on Expression of Socs1, Socs3, Ship1, and Traf6 Genes and Serum Levels of Il-6 and Tnf-Α in Patients With Multiple Sclerosis, Journal of Clinical Pharmacology (2021)
22. Effect of Β-D-Mannuronic Acid (M2000) on Oxidative Stress Enzymes’ Gene Using Healthy Donor Peripheral Blood Mononuclear Cells for Evaluating the Anti-Aging Property, Current Drug Discovery Technologies (2019)
23. The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients, Current Drug Discovery Technologies (2020)
24. Evaluation of Cell Adhesion Molecules (Lfa-1 and L-Selectin) in Ankylosing Spondylitis Patients After Treatment With ß-D-Mannuronic Acid (M2000), Indian Journal of Medical Research (2023)
25. Modification of Sexual Hormones in Rheumatoid Arthritis Patients by M2000 (Β-D-Mannuronic Acid) As a Novel Nsaid With Immunosuppressive Property, Endocrine# Metabolic and Immune Disorders - Drug Targets (2018)
26. Introduction of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property Based on Cox-1/Cox-2 Activity and Gene Expression, Pharmacological Reports (2017)
27. Oral Administration Effects of Β-D-Mannuronic Acid (M2000) on Th17 and Regulatory T Cells in Patients With Ankylosing Spondylitis, Biomedicine and Pharmacotherapy (2018)
28. The Potent Suppressive Effect of Β-D-Mannuronic Acid (M2000) on Molecular Expression of the Tlr/Nf-Kb Signaling Pathway in Ankylosing Spondylitis Patients, International Immunopharmacology (2017)
29. The Potent Inhibitory Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Antidsdna Antibodies in Patients With Rheumatoid Arthritis, Current Drug Discovery Technologies (2017)
30. Immunotherapeutic Effects of Β-D Mannuronic Acid on Il-4, Gata3, Il-17 and Rorc Gene Expression in the Pbmc of Patients With Inflammatory Bowel Diseases, Iranian Journal of Allergy# Asthma and Immunology (2018)
31. Evaluation of the Efficacy and Safety of Β-D-Mannuronic Acid in Patients With Ankylosing Spondylitis: A 12-Week Randomized, Placebo-Controlled, Phase I/Ii Clinical Trial, International Immunopharmacology (2018)
32. Effects of Β-D-Mannuronic Acid, As a Novel Non-Steroidal Anti-Inflammatory Medication Within Immunosuppressive Properties, on Il17, Rorγt, Il4 and Gata3 Gene Expressions in Rheumatoid Arthritis Patients, Drug Design# Development and Therapy (2017)
33. Hematological Improvement of Patients With Active Rheumatoid Arthritis by Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property, Iranian Journal of Allergy# Asthma and Immunology (2017)
34. Immunomodulatory Effects of M2000 (Β-D-Mannuronic Acid) on Tnf-Α, Il-17 and Foxp3 Gene Expression in Patients With Inflammatory Bowel Disease, International Immunopharmacology (2017)
35. Clinical Improvement of Diabetes Mellitus Type 1 by Β-D-Mannuronic Acid (M2000) in a Breast Cancer Patient - As a Case Report, Clinical Diabetology (2019)
36. M2000 (Β-D-Mannuronic Acid) As a Novel Antagonist for Blocking the Tlr2 and Tlr4 Downstream Signalling Pathway, Scandinavian Journal of Immunology (2017)
37. Assessment of Biochemical Determinants in Multiple Sclerosis Patients Following the Oral Administration of Β-D-Mannuronic Acid (M2000), Current Drug Discovery Technologies (2021)
38. Targeting of Crosstalk Between Tumor and Tumor Microenvironment by Β-D Mannuronic Acid (M2000) in Murine Breast Cancer Model, Cancer Medicine (2017)
39. Anti-Angiogenesis Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Properties Under Experimental Model, Clinical and Experimental Pharmacology and Physiology (2018)
40. The Biology of Β-D-Mannuronic Acid (M2000) on Human Dendritic Cell Based on Microrna-155 and Microrna-221, Current Drug Discovery Technologies (2017)
41. Effects of Mannuronic Acid (M2000) on Gene Expression Profile of Signal Transducer and Activator of Transcription Proteins (Stats) in Rheumatoid Arthritis Patients, Reumatismo (2020)
42. The Effects of Β-D-Mannuronic Acid (M2000), As a Novel Nsaid, on Cox1 and Cox2 Activities and Gene Expression in Ankylosing Spondylitis Patients and the Murine Monocyte/Macrophage, J774 Cell Line, Inflammopharmacology (2018)
43. Pharmacological Effects of Β-D-Mannuronic Acid (M2000) on Mir-146A, Irak1, Traf6 and Nf-Κb Gene Expression, As Target Molecules in Inflammatory Reactions, Pharmacological Reports (2017)
44. Targeting of Circulating Th17 Cells by Β-D-Mannuronic Acid (M2000) As a Novel Medication in Patients With Rheumatoid Arthritis, Inflammopharmacology (2018)
45. Preclinical Assessment of Β - D -Mannuronic Acid (M2000) As a Non-Steroidal Anti-Inflammatory Drug, Immunopharmacology and Immunotoxicology (2015)
46. Preclinical and Pharmacotoxicology Evaluation of Α-L-Guluronic Acid (G2013) As a Non-Steroidal Anti-Inflammatory Drug With Immunomodulatory Property, Immunopharmacology and Immunotoxicology (2017)
47. Effects of M2000 (D -Mannuronic Acid) on Learning, Memory Retrieval, and Associated Determinants in a Rat Model of Alzheimer's Disease, American Journal of Alzheimer's Disease and other Dementias (2017)
48. The Effect of Β-D-Mannuronic Acid in Animal Model of Epilepsy, Natural Product Communications (2020)
49. Efficient Roles of Mir-146A in Cellular and Molecular Mechanisms of Neuroinflammatory Disorders: An Effectual Review in Neuroimmunology, Immunology Letters (2021)
50. Anti-Aging Effects of M2000 (Β-D-Mannuronic Acid) As a Novel Immunosuppressive Drug on the Enzymatic and Non-Enzymatic Oxidative Stress Parameters in an Experimental Model, Journal of Basic and Clinical Physiology and Pharmacology (2017)