In Vitro Effects of Sodium Benzoate on the Expression of T Cells-related Cytokines and Transcription Factors in Adjuvant-induced Arthritis Model
Abstract
Though the exact etiology of rheumatoid arthritis (RA) is unknown, the contribution of immune cells in the disease process is completely acknowledged. T helper (Th) 1 and Th17-related cytokines are required for the disease development and progression, while Th2 and regulatory T cells (Tregs)-derived cytokines are protective. Studies have shown that sodium benzoate (NaB) can switch the balance of Th cell subsets toward Th2 and Tregs. The present study aimed to evaluate the possible effects of NaB on the expression of CD4+T cells-related cytokines and transcription factors in splenocytes derived from an animal model of RA, adjuvant-induced arthritis (AIA).
AIA was induced in rats by injection of Freund's adjuvant containing mycobacterial antigens (Mtb). Splenocytes were isolated from AIA rats and restimulated ex vivo with Mtb in the presence or absence of NaB for 24 h. To determine the effects of NaB on the expression of T cells-related cytokine and transcription factor genes, real-time PCR was performed.
NaB treatment of Mtb-stimulated splenocytes derived from arthritic rats resulted in significant increases in the gene expressions of Tregs-related cytokines (IL-10 and TGF-β) and Foxp3 transcription factor, and significant decreases in the expression of Th1-related cytokines (TNF-α and IFN-γ) and the T-bet transcription factor. The ratios of Th1/Th2 (IFN-γ/IL-4), Th1/Treg (IFN-γ/TGF-β and IFN-γ/IL-10) and Th17/Treg (IL-17/IL-10 and IL-17/IL-10+TGF-β)-related cytokines were also significantly decreased.
In conclusion, NaB can potentially be considered as a useful therapeutic agent for the treatment of RA and other Th1 and Th17-mediated diseases.
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4. Al-Saadany HM, Hussein MS, Gaber RA, Zaytoun HA. Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity. The Egyptian Rheumatologist. 2016;38(1):1-7.
5. Wiesenberg I, Van der Meide PH, Schellekens H, Alkan S. Suppression and augmentation of rat adjuvant arthritis with monoclonal anti-interferon-gamma antibody. Clin Exp Immunol. 1989;78(2):245-9
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7. Haas CS, Amin MA, Allen BB, Ruth JH, Haines GK, 3rd, Woods JM, et al. Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis. Arthritis Rheum. 2006;54(8):2402-14.
8. Ren Q, Meng T, Lin C, Du C, Liu T, Wang J, et al. Effect of human recombinant interleukin-10 on cytokines in adjuvant arthritis rat. Int J Clin Exp Pathol. 2016;9(5):5606-10.
9. Chang Y, Wu Y, Wang D, Wei W, Qin Q, Xie G, et al. Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via attenuating inflammatory responses. Rheumatology. 2010;50(5):862-70.
10. Negrei C, Bojinca V, Balanescu A, Bojinca M, et al. Management of rheumatoid arthritis: Impact and risks of various therapeutic approaches (Review). Experimental and therapeutic medicine. 2016;11(4):1177-83.
11. Jana A, Modi KK, Roy A, Anderson JA, Van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. Journal of Neuroimmune Pharmacology. 2013;8(3):739-55.
12. Misel ML, Gish RG, Patton H, Mendler M. Sodium benzoate for treatment of hepatic encephalopathy. Gastroenterology and hepatology. 2013;9(4):219.
13. Rezaei N, Amirghofran Z, Nikseresht A, Ashjazade N, Zoghi S, Tahvili S, et al. In Vitro Effects of Sodium Benzoate on Th1/Th2 Deviation in Patients with Multiple Sclerosis. Immunological Investigations. 2016;45(7):679-91.
14. Brahmachari S, Pahan K. Sodium benzoate, a food additive and a metabolite of cinnamon, modifies T cells at multiple steps and inhibits adoptive transfer of experimental allergic encephalomyelitis. The Journal of Immunology. 2007;179(1):275-83.
15. Maier E, Kurz K, Jenny M, Schennach H, Ueberall F, Fuchs D. Food preservatives sodium benzoate and propionic acid and colorant curcumin suppress Th1-type immune response in vitro. Food and chemical toxicology. 2010;48(7):1950-6.
16. Pacor M, Di Lorenzo G, Martinelli N, Mansueto P, Rini G, Corrocher R. Monosodium benzoate hypersensitivity in subjects with persistent rhinitis. Allergy. 2004;59(2):192-7.
17. Cai X, Wong YF, Zhou H, Xie Y, Liu ZQ, Jiang ZH, et al. The comparative study of Sprague-Dawley and Lewis rats in adjuvant-induced arthritis. Naunyn Schmiedebergs Arch Pharmacol. 2006;373(2):140-7.
18. Wang T, Li S, Yang Y, Zhang K, Dong S, Wang X, et al. T helper 17 and T helper 1 cells are increased but regulatory T cells are decreased in subchondral bone marrow microenvironment of patients with rheumatoid arthritis. Am J Translat Res. 2016;8(7):2956-68.
19. Cooles FA, Isaacs JD, Anderson AE. Treg cells in rheumatoid arthritis: an update. Current rheumatology reports. 2013;15(9):1-9.
20. Davis LS, Cush JJ, Schulze-Koops H, Lipsky PE. Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells. Arthritis Res. 2001;3(1):54-64.
21. Kundu M, Mondal S, Roy A, Martinson JL, Pahan K. Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β. J Immunol. 2016;197(8):3099-110.
22. Yadav A, Kumar A, Das M, Tripathi A. Sodium benzoate, a food preservative, affects the functional and activation status of splenocytes at non cytotoxic dose. Food Chem Toxicol. 2016;88:40-7.
23. Dolhain RJEM, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AMM. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis & Rheumatism. 1996;39(12):1961-9.
24. He C, Feng P, Su H, Gu A, Yan Z, Zhu X. Disrupted Th1/Th2 balance in patients with
rheumatoid arthritis (RA). Int J Clin Exp Pathol. 2017;10(2):1233-42.
25. Lina C, Conghua W, Nan L, Ping Z. Combined treatment of etanercept and MTX reverses Th1/Th2, Th17/Treg imbalance in patients with rheumatoid arthritis. J Clin Immunol. 2011;31(4):596-605.
26. Qian C, Kuang M, Wang Y. Effect of qianghuo erhuang decoction on T regulatory and T helper 17 cells in treatment of adjuvant-induced arthritis in rats. Scientific reports. 2017;7(1):17198.
27. Ahmad SF, Khan B, Bani S, Suri K, Satti N, Qazi G. Amelioration of adjuvant-induced arthritis by ursolic acid through altered Th1/Th2 cytokine production. Pharmacological research. 2006;53(3):233-40.
28. Gaafar T, Farid R, Raafat H, Bayoumi F, Gerges B, Rasheed D. The TH17/Treg imbalance in rheumatoid arthritis and relation to disease activity. J Clin Cell Immunol. 2015;6(6).
29. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. New England Journal of Medicine. 2011;365(23):2205-19.
30. Gao Y, Grassi F, Ryan MR, Terauchi M, Page K, Yang X, et al. IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. The Journal of clinical investigation. 2007;117(1):122-32.
31. Chen Z, Andreev D, Oeser K, Krljanac B, Hueber A, Kleyer A, et al. Th2 and eosinophil responses suppress inflammatory arthritis. Nature communications. 2016;7:11596.
32. Chen Z, Bozec A, Ramming A, Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2019;15(1):9-17.
33. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. Journal of Experimental Medicine. 2006;203(12):2673-82.
34. Robert M, Miossec P. IL-17 in Rheumatoid Arthritis and Precision Medicine: From Synovitis Expression to Circulating Bioactive Levels. Frontiers in medicine. 2019;5:364-.
35. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunology. 2007;7(6):429-42.
36. Park-Min K-H, Ji J-D, Antoniv T, Reid AC, Silver RB, Humphrey MB, et al. IL-10 suppresses calcium-mediated costimulation of receptor activator NF-kappa B signaling during human osteoclast differentiation by inhibiting TREM-2 expression. Journal of immunology (Baltimore, Md : 1950). 2009;183(4):2444-55.
37. Kelchtermans H, Geboes L, Mitera T, Huskens D, Leclercq G, Matthys P. Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis. Ann Rheum Dis. 2009;68(5):744-50.
38. Khasnavis S, Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, upregulates neuroprotective Parkinson disease protein DJ-1 in astrocytes and neurons. Journal of neuroimmune pharmacology. 2012;7(2):424-35.
39. Pongsavee M. Effect of sodium benzoate preservative on micronucleus induction, chromosome break, and ala40thr superoxide dismutase gene mutation in lymphocytes. BioMed Res Inter. 2015;2015.
2. Vyas SP, Hansda AK, Goswami R. Rheumatoid arthritis: 'melting pot' of T helper subsets. Int Rev Immunol. 2019;38(5):212-31.
3. Croia C, Bursi R, Sutera D, Petrelli F, Alunno A, Puxeddu I. One year in review 2019: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2019;37(3):347-57.
4. Al-Saadany HM, Hussein MS, Gaber RA, Zaytoun HA. Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity. The Egyptian Rheumatologist. 2016;38(1):1-7.
5. Wiesenberg I, Van der Meide PH, Schellekens H, Alkan S. Suppression and augmentation of rat adjuvant arthritis with monoclonal anti-interferon-gamma antibody. Clin Exp Immunol. 1989;78(2):245-9
6. Bush KA, Farmer KM, Walker JS, Kirkham BW. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin‐17 receptor IgG1 Fc fusion protein. Arthritis and Rheumatism. 2002;46(3):802-5.
7. Haas CS, Amin MA, Allen BB, Ruth JH, Haines GK, 3rd, Woods JM, et al. Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis. Arthritis Rheum. 2006;54(8):2402-14.
8. Ren Q, Meng T, Lin C, Du C, Liu T, Wang J, et al. Effect of human recombinant interleukin-10 on cytokines in adjuvant arthritis rat. Int J Clin Exp Pathol. 2016;9(5):5606-10.
9. Chang Y, Wu Y, Wang D, Wei W, Qin Q, Xie G, et al. Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via attenuating inflammatory responses. Rheumatology. 2010;50(5):862-70.
10. Negrei C, Bojinca V, Balanescu A, Bojinca M, et al. Management of rheumatoid arthritis: Impact and risks of various therapeutic approaches (Review). Experimental and therapeutic medicine. 2016;11(4):1177-83.
11. Jana A, Modi KK, Roy A, Anderson JA, Van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. Journal of Neuroimmune Pharmacology. 2013;8(3):739-55.
12. Misel ML, Gish RG, Patton H, Mendler M. Sodium benzoate for treatment of hepatic encephalopathy. Gastroenterology and hepatology. 2013;9(4):219.
13. Rezaei N, Amirghofran Z, Nikseresht A, Ashjazade N, Zoghi S, Tahvili S, et al. In Vitro Effects of Sodium Benzoate on Th1/Th2 Deviation in Patients with Multiple Sclerosis. Immunological Investigations. 2016;45(7):679-91.
14. Brahmachari S, Pahan K. Sodium benzoate, a food additive and a metabolite of cinnamon, modifies T cells at multiple steps and inhibits adoptive transfer of experimental allergic encephalomyelitis. The Journal of Immunology. 2007;179(1):275-83.
15. Maier E, Kurz K, Jenny M, Schennach H, Ueberall F, Fuchs D. Food preservatives sodium benzoate and propionic acid and colorant curcumin suppress Th1-type immune response in vitro. Food and chemical toxicology. 2010;48(7):1950-6.
16. Pacor M, Di Lorenzo G, Martinelli N, Mansueto P, Rini G, Corrocher R. Monosodium benzoate hypersensitivity in subjects with persistent rhinitis. Allergy. 2004;59(2):192-7.
17. Cai X, Wong YF, Zhou H, Xie Y, Liu ZQ, Jiang ZH, et al. The comparative study of Sprague-Dawley and Lewis rats in adjuvant-induced arthritis. Naunyn Schmiedebergs Arch Pharmacol. 2006;373(2):140-7.
18. Wang T, Li S, Yang Y, Zhang K, Dong S, Wang X, et al. T helper 17 and T helper 1 cells are increased but regulatory T cells are decreased in subchondral bone marrow microenvironment of patients with rheumatoid arthritis. Am J Translat Res. 2016;8(7):2956-68.
19. Cooles FA, Isaacs JD, Anderson AE. Treg cells in rheumatoid arthritis: an update. Current rheumatology reports. 2013;15(9):1-9.
20. Davis LS, Cush JJ, Schulze-Koops H, Lipsky PE. Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells. Arthritis Res. 2001;3(1):54-64.
21. Kundu M, Mondal S, Roy A, Martinson JL, Pahan K. Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β. J Immunol. 2016;197(8):3099-110.
22. Yadav A, Kumar A, Das M, Tripathi A. Sodium benzoate, a food preservative, affects the functional and activation status of splenocytes at non cytotoxic dose. Food Chem Toxicol. 2016;88:40-7.
23. Dolhain RJEM, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AMM. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis & Rheumatism. 1996;39(12):1961-9.
24. He C, Feng P, Su H, Gu A, Yan Z, Zhu X. Disrupted Th1/Th2 balance in patients with
rheumatoid arthritis (RA). Int J Clin Exp Pathol. 2017;10(2):1233-42.
25. Lina C, Conghua W, Nan L, Ping Z. Combined treatment of etanercept and MTX reverses Th1/Th2, Th17/Treg imbalance in patients with rheumatoid arthritis. J Clin Immunol. 2011;31(4):596-605.
26. Qian C, Kuang M, Wang Y. Effect of qianghuo erhuang decoction on T regulatory and T helper 17 cells in treatment of adjuvant-induced arthritis in rats. Scientific reports. 2017;7(1):17198.
27. Ahmad SF, Khan B, Bani S, Suri K, Satti N, Qazi G. Amelioration of adjuvant-induced arthritis by ursolic acid through altered Th1/Th2 cytokine production. Pharmacological research. 2006;53(3):233-40.
28. Gaafar T, Farid R, Raafat H, Bayoumi F, Gerges B, Rasheed D. The TH17/Treg imbalance in rheumatoid arthritis and relation to disease activity. J Clin Cell Immunol. 2015;6(6).
29. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. New England Journal of Medicine. 2011;365(23):2205-19.
30. Gao Y, Grassi F, Ryan MR, Terauchi M, Page K, Yang X, et al. IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. The Journal of clinical investigation. 2007;117(1):122-32.
31. Chen Z, Andreev D, Oeser K, Krljanac B, Hueber A, Kleyer A, et al. Th2 and eosinophil responses suppress inflammatory arthritis. Nature communications. 2016;7:11596.
32. Chen Z, Bozec A, Ramming A, Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2019;15(1):9-17.
33. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. Journal of Experimental Medicine. 2006;203(12):2673-82.
34. Robert M, Miossec P. IL-17 in Rheumatoid Arthritis and Precision Medicine: From Synovitis Expression to Circulating Bioactive Levels. Frontiers in medicine. 2019;5:364-.
35. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunology. 2007;7(6):429-42.
36. Park-Min K-H, Ji J-D, Antoniv T, Reid AC, Silver RB, Humphrey MB, et al. IL-10 suppresses calcium-mediated costimulation of receptor activator NF-kappa B signaling during human osteoclast differentiation by inhibiting TREM-2 expression. Journal of immunology (Baltimore, Md : 1950). 2009;183(4):2444-55.
37. Kelchtermans H, Geboes L, Mitera T, Huskens D, Leclercq G, Matthys P. Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis. Ann Rheum Dis. 2009;68(5):744-50.
38. Khasnavis S, Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, upregulates neuroprotective Parkinson disease protein DJ-1 in astrocytes and neurons. Journal of neuroimmune pharmacology. 2012;7(2):424-35.
39. Pongsavee M. Effect of sodium benzoate preservative on micronucleus induction, chromosome break, and ala40thr superoxide dismutase gene mutation in lymphocytes. BioMed Res Inter. 2015;2015.
| Files | ||
| Issue | Vol 19, No S1 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v19i(s1.r1).2853 | |
| PMID | 32534510 | |
| Keywords | ||
| Adjuvant-induced arthritis CD4 T cells Cytokines Sodium benzoate Transcription factors | ||
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How to Cite
1.
Bemani P, Amirghofran Z, Kamali-Sarvestani E. In Vitro Effects of Sodium Benzoate on the Expression of T Cells-related Cytokines and Transcription Factors in Adjuvant-induced Arthritis Model. Iran J Allergy Asthma Immunol. 2020;19(S1):43-54.
