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
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 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.
1. Brzustewicz E, Bryl E. The role of cytokines in the pathogenesis of rheumatoid arthritis–Practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine. 2015;76(2):527-36.
2. Pablos JL. Rheumatoid Arthritis. LANCET. 2016.
3. Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207-9.
4. Bystrom J, Clanchy F, Taher TE, Mangat P, Jawad AS, Williams RO, et al. TNFα in the regulation of Treg and Th17 cells in rheumatoid arthritis and other autoimmune inflammatory diseases. Cytokine. 2018;101(21):4-13.
5. Chaabo K, Kirkham B. Rheumatoid arthritis—anti-TNF. Int Immunopharmacol. 2015;27(2):180-4.
6. Connor AM, Mahomed N, Gandhi R, Keystone EC, Berger SA. TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther.2012;14(2):R62.
7. Zheng Y, Sun L, Jiang T, Zhang D, He D, Nie H. TNFα promotes Th17 cell differentiation through IL-6 and IL-1β produced by monocytes in rheumatoid arthritis. J Immunol Res. 2014;2014:373252.
8. Muller N, Schulte DM, Turk K, Freitag-Wolf S, Hampe J, Zeuner R, et al. IL-6 blockade by monoclonal antibodies inhibits apolipoprotein (a) expression and lipoprotein (a) synthesis in humans. J Lipid Res. 2015;56(5):1034-42.
9. Fleischer S, Ries S, Shen P, Lheritier A, Cazals F, Burmester GR, et al. Anti‐interleukin‐6 signalling therapy rebalances the disrupted cytokine production of B cells from patients with active rheumatoid arthritis. Eur J Immunol. 2018;48(1):194-203.
10. Eser B, Sahin N. Evaluation of tool-like receptor-2 and 4 and interleukin-6 gene expressions in Turkish rheumatoid arthritis patients. Clin Rheumatol.. 2016;35(11):2693-7.
11. Karim AF, Reba SM, Li Q, Boom WH, Rojas RE. Toll like Receptor 2 engagement on CD4+ T cells promotes TH9 differentiation and function. Eur J Immunol. 2017;47(9):1513-24.
12. Quero L, Hanser E, Manigold T, Tiaden AN, Kyburz D. TLR2 stimulation impairs anti-inflammatory activity of M2-like macrophages, generating a chimeric.
13. Mirshafiey A, Rehm B, Sotoude M, Razavi A, Abhari RS, Borzooy Z. Therapeutic approach by a novel designed anti-inflammatory drug, M2000, in experimental immune complex glomerulonephritis. Immunopharmacol Immunotoxicol. 2007;29(1):49-61.
14. Rezaieyazdi Z, Farooqi A, Soleymani-Salehabadi H, Ahmadzadeh A, Aslani M, Omidian S, et al. International multicenter randomized, placebo-controlled phase III clinical trial of β-d-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacology. 2019;7(5):1-11.
15. Bakhtiari T, Ghaderi A, Safaee Nodehi SR, Aghazadeh Z, Tofighi Zavareh F, Jafarnezhad‐Ansariha F, et al. An in vitro assessment for evaluating the efficiency of β‐d‐mannuronic acid (M2000) in myelodysplastic syndrome. J Cell Physiol. 2019;234(8):12971-7.
16. Fattahi MJ, Abdollahi M, Agha Mohammadi A, Rastkari N, Khorasani R, Ahmadi H, et al. Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacol Immunotoxicol. 2015;37(6):535-40.
17. Mirshafiey A, Rehm B, Cuzzocrea S, Matsuo H, Mazzon E, Nakane S, et al. M2000, foundation of a new generation among NSAIDs. Letters in Drug Design & Discovery. 2005;2(5):412-23.
18. Taeb M, Jafarzadeh A, Mortazavi-Jahromi S, Zainodini N, Mirzaei M, Jafarnezhad-Ansariha F, et al. 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. Curr Drug Discov Technol. 2019;16(3):265-71.
19. Mortazavi-Jahromi SS, Alizadeh S, Javanbakht MH, Mirshafiey A. 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.Arch Physiol Biochem. 2018;125(5):1-6.
20. Rastegari-Pouyani M, Mostafaie A, Mansouri K, Mortazavi-Jahromi SS, Mohammadi-Motlagh HR, Mirshafiey A. Anti-angiogenesis effect of beta-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model. Clin Exp Pharmacol Physiol. 2018;45(4):370-6.
21. Jahanbakhshi M, Babaloo Z, Mortazavi-Jahromi S, Shokri M, Ahmadi H, Mirshafiey A. Modification of sexual hormones in rheumatoid arthritis patients by M2000 (β-D-mannuronic acid) as a novel NSAID with immunosuppressive property. Endocrine, metabolic & immune disorders drug targets. 2018;18(5):530-6.
22. Farahani MM, Motevaseli E, Maghsood F, Heidari-Kharaji M, Mirshafiey A. Anti-inflammatory property of β-D-mannuronic acid (M2000) on expression and activity of matrix metalloproteinase-2 and-9 through CD147 molecule in phorbol myristate acetate-differentiated THP-1 cells. Iran J Allergy Asthma Immunol. 2017;16(5):443-51.
23. Jafarnezhad-Ansariha F, Yekaninejad MS, Jamshidi A-r, Mansouri R, Vojdanian M, Mahmoudi M, et al. 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;26(2):375-84.
24. Tabrizian N, Arjomand Fard N, Farazmand A, Eftekhari R, Tofighi Zavareh F, Mirshafiey A. The Biology of β-D-mannuronic acid (M2000) on Human Dendritic Cell Based on MicroRNA-155 and MicroRNA-221. Curr Drug Discov Technol. 2017;14(1):53-8.
25. Ahmadi H, Jamshidi AR, Gharibdoost F, Mahmoudi M, Rastkari N, Mostafaei S, et al. 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;26(3):733-45.
26. Ahmadi H, Mahmoudi M, Gharibdoost F, Vojdanian M, reza Jamshidi A, javad Fattahi M, et al. Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis. Inflammopharmacology. 2018;26(1):57-65.
27. Barati A, Jamshidi AR, Ahmadi H, Aghazadeh Z, Mirshafiey A. 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 Des Devel Ther. 2017;11(4):1027-32.
28. Fattahi MJ, Jamshidi AR, Mahmoudi M, Vojdanian M, Yekaninejad MS, Jafarnezhad-Ansariha F, et al. 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. Int Immunopharmacol. 2018;54(5):112-7.
29. Fattahi MJ, Ahmadi H, Jafarnezhad-Ansariha F, Mortazavi-Jahromi SS, Rehm BH, Cuzzocrea S, et al. Oral administration effects of β-d-mannuronic acid (M2000) on Th17 and regulatory T cells in patients with ankylosing spondylitis. Biomedicine & Pharmacotherapy. 2018;100(41):495-500.
30. Ahmadi H, Jamshidi AR, Mahmoudi M, Cuzzocrea S, Fattahi MJ, Barati A, et al. 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 anti-dsDNA antibodies in patients with rheumatoid arthritis. Curr Drug Discov Technol. 2017;14(3):206-14.
31. M-Tago F, Shimizu T, Tago K.Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB. Biochem Pharmacol. 2008;76(5):662-71.
32. Huang Z, Jiang H, Zhao H, Liu Z, Dong Z, Zhu B. Efficacy of parecoxib on the level of IL-6, CRP and postoperative pain relief after percutaneous nephrolithotomy.Int J Clin Exp Med. 2016;9(10):19454-60.
33. Gorsky VA, Agapov MA, Khoreva MV, Leonenko IV. The effect of lornoxicam on TLR2 and TLR4 messenger RNA expression and tumor necrosis factor-α, interleukin-6, and interleukin-8 secretion in patients with systemic complications of acute pancreatitis. Pancreas. 2015;44(5):824-30.
34. Barcelos RP, Bresciani G, Cuevas MJ, Martínez-Flórez S, Soares FAA, González-Gallego J. Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway. Appl Physiol Nutr Metabm. 2017;42(7):757-64.
35. Abdollahi-Roodsaz S, Joosten LA, Koenders MI, Devesa I, Roelofs MF, Radstake TR, et al. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest. 2008;118(1):205-16.
36. Sahaya Sangeetha S, Devi R, Esther Nalini H, Kumar A. Toll-like receptors: The gateway of immune system. 2018.
37. Ji-Qing Chen M, Peter Szodoray M, Margit Zeher M. Toll-like receptor pathways in autoimmune diseases. Springer. 1–17(2016).
38. Lacerte P, Brunet A, Egarnes B, Duchêne B, Brown JP, Gosselin J. Overexpression of TLR2 and TLR9 on monocyte subsets of active rheumatoid arthritis patients contributes to enhance responsiveness to TLR agonists. Arthritis Res Ther. 2016;18(1):10-6.
39. Saber T, Veale DJ, Balogh E, McCormick J, NicAnUltaigh S, Connolly M, et al. Toll-like receptor 2 induced angiogenesis and invasion is mediated through the Tie2 signalling pathway in rheumatoid arthritis. PloS One. 2011;6(8):e23540.
40. Aletaha S, Haddad L, Roozbehkia M, Bigdeli R, Asgary V, Mahmoudi M, et al. M2000 (β‐D‐Mannuronic Acid) as a Novel Antagonist for Blocking the TLR 2 and TLR 4 Downstream Signalling Pathway. Scandinavian J Immunol. 2017;85(2):122-9.
41. Roozbehkia M, Mahmoudi M, Aletaha S, Rezaei N, Fattahi MJ, Jafarnezhad-Ansariha F, et al. The potent suppressive effect of beta-d-mannuronic acid (M2000) on molecular expression of the TLR/NF-kB Signaling Pathway in ankylosing spondylitis patients. Int Immunopharmacol. 2017;52(4):191-6.
42. Mortazavi-Jahromi SS, Ahmadzadeh A, Rezaieyazdi Z. 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. Immunopharmacol Immunotoxicol. 2020;423;10:1080.
43. Mortazavi-Jahromi SS, Jamshidi MM, et al. Pharmacological effects of βd-mannuronic acid (M2000) on miR-146a, IRAK-1, TRAF6 and NF-KB gene expression, as target molecules in inflammatory reactions. Pharmacol Rep. 2017;69(3): 479-484.
44. Tanimura A, Nakazato A, Tanaka N. MYD88 signals induce tumour-initiating cell generation through the NF-κB-HIF-1α activation cascade. Sci Rep. 2021;11(1):3991-9.
45. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology. 2012;51(suppl-5):v3-v11.
46. Yoshida Y, Tanaka T. Interleukin 6 and rheumatoid arthritis. BioMed Research International. 2014;2014:215477.
47. Aslani M, Ahmadzadeh A, Aghazadeh Z. 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. Curr Drug Discov Technol. 2021;18(1):65-74.
48. Mortazavi‐Jahromi SS. Aslani M, Omidian S. 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 Dev Res;2020;81(3):295-304.
49. Gaafar N, Aslani M, Aghazadeh Z. Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and activator of transcription proteins (STATs) in rheumatoid arthritis patients. Reumatismo. 2020;72(2):93-102.
2. Pablos JL. Rheumatoid Arthritis. LANCET. 2016.
3. Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207-9.
4. Bystrom J, Clanchy F, Taher TE, Mangat P, Jawad AS, Williams RO, et al. TNFα in the regulation of Treg and Th17 cells in rheumatoid arthritis and other autoimmune inflammatory diseases. Cytokine. 2018;101(21):4-13.
5. Chaabo K, Kirkham B. Rheumatoid arthritis—anti-TNF. Int Immunopharmacol. 2015;27(2):180-4.
6. Connor AM, Mahomed N, Gandhi R, Keystone EC, Berger SA. TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther.2012;14(2):R62.
7. Zheng Y, Sun L, Jiang T, Zhang D, He D, Nie H. TNFα promotes Th17 cell differentiation through IL-6 and IL-1β produced by monocytes in rheumatoid arthritis. J Immunol Res. 2014;2014:373252.
8. Muller N, Schulte DM, Turk K, Freitag-Wolf S, Hampe J, Zeuner R, et al. IL-6 blockade by monoclonal antibodies inhibits apolipoprotein (a) expression and lipoprotein (a) synthesis in humans. J Lipid Res. 2015;56(5):1034-42.
9. Fleischer S, Ries S, Shen P, Lheritier A, Cazals F, Burmester GR, et al. Anti‐interleukin‐6 signalling therapy rebalances the disrupted cytokine production of B cells from patients with active rheumatoid arthritis. Eur J Immunol. 2018;48(1):194-203.
10. Eser B, Sahin N. Evaluation of tool-like receptor-2 and 4 and interleukin-6 gene expressions in Turkish rheumatoid arthritis patients. Clin Rheumatol.. 2016;35(11):2693-7.
11. Karim AF, Reba SM, Li Q, Boom WH, Rojas RE. Toll like Receptor 2 engagement on CD4+ T cells promotes TH9 differentiation and function. Eur J Immunol. 2017;47(9):1513-24.
12. Quero L, Hanser E, Manigold T, Tiaden AN, Kyburz D. TLR2 stimulation impairs anti-inflammatory activity of M2-like macrophages, generating a chimeric.
13. Mirshafiey A, Rehm B, Sotoude M, Razavi A, Abhari RS, Borzooy Z. Therapeutic approach by a novel designed anti-inflammatory drug, M2000, in experimental immune complex glomerulonephritis. Immunopharmacol Immunotoxicol. 2007;29(1):49-61.
14. Rezaieyazdi Z, Farooqi A, Soleymani-Salehabadi H, Ahmadzadeh A, Aslani M, Omidian S, et al. International multicenter randomized, placebo-controlled phase III clinical trial of β-d-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacology. 2019;7(5):1-11.
15. Bakhtiari T, Ghaderi A, Safaee Nodehi SR, Aghazadeh Z, Tofighi Zavareh F, Jafarnezhad‐Ansariha F, et al. An in vitro assessment for evaluating the efficiency of β‐d‐mannuronic acid (M2000) in myelodysplastic syndrome. J Cell Physiol. 2019;234(8):12971-7.
16. Fattahi MJ, Abdollahi M, Agha Mohammadi A, Rastkari N, Khorasani R, Ahmadi H, et al. Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacol Immunotoxicol. 2015;37(6):535-40.
17. Mirshafiey A, Rehm B, Cuzzocrea S, Matsuo H, Mazzon E, Nakane S, et al. M2000, foundation of a new generation among NSAIDs. Letters in Drug Design & Discovery. 2005;2(5):412-23.
18. Taeb M, Jafarzadeh A, Mortazavi-Jahromi S, Zainodini N, Mirzaei M, Jafarnezhad-Ansariha F, et al. 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. Curr Drug Discov Technol. 2019;16(3):265-71.
19. Mortazavi-Jahromi SS, Alizadeh S, Javanbakht MH, Mirshafiey A. 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.Arch Physiol Biochem. 2018;125(5):1-6.
20. Rastegari-Pouyani M, Mostafaie A, Mansouri K, Mortazavi-Jahromi SS, Mohammadi-Motlagh HR, Mirshafiey A. Anti-angiogenesis effect of beta-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model. Clin Exp Pharmacol Physiol. 2018;45(4):370-6.
21. Jahanbakhshi M, Babaloo Z, Mortazavi-Jahromi S, Shokri M, Ahmadi H, Mirshafiey A. Modification of sexual hormones in rheumatoid arthritis patients by M2000 (β-D-mannuronic acid) as a novel NSAID with immunosuppressive property. Endocrine, metabolic & immune disorders drug targets. 2018;18(5):530-6.
22. Farahani MM, Motevaseli E, Maghsood F, Heidari-Kharaji M, Mirshafiey A. Anti-inflammatory property of β-D-mannuronic acid (M2000) on expression and activity of matrix metalloproteinase-2 and-9 through CD147 molecule in phorbol myristate acetate-differentiated THP-1 cells. Iran J Allergy Asthma Immunol. 2017;16(5):443-51.
23. Jafarnezhad-Ansariha F, Yekaninejad MS, Jamshidi A-r, Mansouri R, Vojdanian M, Mahmoudi M, et al. 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;26(2):375-84.
24. Tabrizian N, Arjomand Fard N, Farazmand A, Eftekhari R, Tofighi Zavareh F, Mirshafiey A. The Biology of β-D-mannuronic acid (M2000) on Human Dendritic Cell Based on MicroRNA-155 and MicroRNA-221. Curr Drug Discov Technol. 2017;14(1):53-8.
25. Ahmadi H, Jamshidi AR, Gharibdoost F, Mahmoudi M, Rastkari N, Mostafaei S, et al. 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;26(3):733-45.
26. Ahmadi H, Mahmoudi M, Gharibdoost F, Vojdanian M, reza Jamshidi A, javad Fattahi M, et al. Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis. Inflammopharmacology. 2018;26(1):57-65.
27. Barati A, Jamshidi AR, Ahmadi H, Aghazadeh Z, Mirshafiey A. 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 Des Devel Ther. 2017;11(4):1027-32.
28. Fattahi MJ, Jamshidi AR, Mahmoudi M, Vojdanian M, Yekaninejad MS, Jafarnezhad-Ansariha F, et al. 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. Int Immunopharmacol. 2018;54(5):112-7.
29. Fattahi MJ, Ahmadi H, Jafarnezhad-Ansariha F, Mortazavi-Jahromi SS, Rehm BH, Cuzzocrea S, et al. Oral administration effects of β-d-mannuronic acid (M2000) on Th17 and regulatory T cells in patients with ankylosing spondylitis. Biomedicine & Pharmacotherapy. 2018;100(41):495-500.
30. Ahmadi H, Jamshidi AR, Mahmoudi M, Cuzzocrea S, Fattahi MJ, Barati A, et al. 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 anti-dsDNA antibodies in patients with rheumatoid arthritis. Curr Drug Discov Technol. 2017;14(3):206-14.
31. M-Tago F, Shimizu T, Tago K.Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB. Biochem Pharmacol. 2008;76(5):662-71.
32. Huang Z, Jiang H, Zhao H, Liu Z, Dong Z, Zhu B. Efficacy of parecoxib on the level of IL-6, CRP and postoperative pain relief after percutaneous nephrolithotomy.Int J Clin Exp Med. 2016;9(10):19454-60.
33. Gorsky VA, Agapov MA, Khoreva MV, Leonenko IV. The effect of lornoxicam on TLR2 and TLR4 messenger RNA expression and tumor necrosis factor-α, interleukin-6, and interleukin-8 secretion in patients with systemic complications of acute pancreatitis. Pancreas. 2015;44(5):824-30.
34. Barcelos RP, Bresciani G, Cuevas MJ, Martínez-Flórez S, Soares FAA, González-Gallego J. Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway. Appl Physiol Nutr Metabm. 2017;42(7):757-64.
35. Abdollahi-Roodsaz S, Joosten LA, Koenders MI, Devesa I, Roelofs MF, Radstake TR, et al. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest. 2008;118(1):205-16.
36. Sahaya Sangeetha S, Devi R, Esther Nalini H, Kumar A. Toll-like receptors: The gateway of immune system. 2018.
37. Ji-Qing Chen M, Peter Szodoray M, Margit Zeher M. Toll-like receptor pathways in autoimmune diseases. Springer. 1–17(2016).
38. Lacerte P, Brunet A, Egarnes B, Duchêne B, Brown JP, Gosselin J. Overexpression of TLR2 and TLR9 on monocyte subsets of active rheumatoid arthritis patients contributes to enhance responsiveness to TLR agonists. Arthritis Res Ther. 2016;18(1):10-6.
39. Saber T, Veale DJ, Balogh E, McCormick J, NicAnUltaigh S, Connolly M, et al. Toll-like receptor 2 induced angiogenesis and invasion is mediated through the Tie2 signalling pathway in rheumatoid arthritis. PloS One. 2011;6(8):e23540.
40. Aletaha S, Haddad L, Roozbehkia M, Bigdeli R, Asgary V, Mahmoudi M, et al. M2000 (β‐D‐Mannuronic Acid) as a Novel Antagonist for Blocking the TLR 2 and TLR 4 Downstream Signalling Pathway. Scandinavian J Immunol. 2017;85(2):122-9.
41. Roozbehkia M, Mahmoudi M, Aletaha S, Rezaei N, Fattahi MJ, Jafarnezhad-Ansariha F, et al. The potent suppressive effect of beta-d-mannuronic acid (M2000) on molecular expression of the TLR/NF-kB Signaling Pathway in ankylosing spondylitis patients. Int Immunopharmacol. 2017;52(4):191-6.
42. Mortazavi-Jahromi SS, Ahmadzadeh A, Rezaieyazdi Z. 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. Immunopharmacol Immunotoxicol. 2020;423;10:1080.
43. Mortazavi-Jahromi SS, Jamshidi MM, et al. Pharmacological effects of βd-mannuronic acid (M2000) on miR-146a, IRAK-1, TRAF6 and NF-KB gene expression, as target molecules in inflammatory reactions. Pharmacol Rep. 2017;69(3): 479-484.
44. Tanimura A, Nakazato A, Tanaka N. MYD88 signals induce tumour-initiating cell generation through the NF-κB-HIF-1α activation cascade. Sci Rep. 2021;11(1):3991-9.
45. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology. 2012;51(suppl-5):v3-v11.
46. Yoshida Y, Tanaka T. Interleukin 6 and rheumatoid arthritis. BioMed Research International. 2014;2014:215477.
47. Aslani M, Ahmadzadeh A, Aghazadeh Z. 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. Curr Drug Discov Technol. 2021;18(1):65-74.
48. Mortazavi‐Jahromi SS. Aslani M, Omidian S. 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 Dev Res;2020;81(3):295-304.
49. Gaafar N, Aslani M, Aghazadeh Z. Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and activator of transcription proteins (STATs) in rheumatoid arthritis patients. Reumatismo. 2020;72(2):93-102.
| Files | ||
| Issue | Vol 21 No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i1.8612 | |
| Keywords | ||
| Interleukin-6 Mannuronic acid MYD88 deficiency Toll-like receptor 2 Tumor necrosis factor-alpha | ||
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How to Cite
1.
Omidian S, Aghazadeh Z, Ahmadzadeh A, Aslani M, Hosseini M, Abbasi S, Mirshafiey A. Evaluating Mannuronic Acid Effect on Gene Expression Profile of Inflammatory Mediators in Rheumatoid Arthritis Patients. Iran J Allergy Asthma Immunol. 2022;21(1):44-54.
