Curcumin-mediated Modulation of T-bet and CD8+ T Cells: A Potential Anti-inflammatory Mechanism in Knee Osteoarthritis
-
Mohsen Ghoryani
,
Soroush Gorgani
,
Mahdi Atabaki
,
Elmira Noori
,
Zhaleh Shariati-Sarabi
,
Mojgan Mohammadi
Abstract
Osteoarthritis (OA) is the most common form of arthritis, characterized by pathological changes in joint components. Increasing evidence suggests that helper T (TH) lymphocytes play a pivotal role in the inflammatory processes associated with OA. Curcumin, the primary polyphenolic compound found in Curcuma longa, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of curcumin on the gene expression of key transcription factors of TH1 and TH2 cells and to explore their associations with clinical and immunological parameters in patients with knee OA.
This mechanistic sub-study presents a secondary molecular analysis of RNA biospecimens from a previously completed double-blind, placebo-controlled clinical trial involving 30 patients with knee OA. Participants were randomly assigned to receive either 80 mg/day of nano-micelle curcumin or a placebo for 3 months. Expression levels of T-box transcription factor 21 (T-bet) and GATA binding protein 3 (GATA3), the key transcription factors of TH1 and TH2 cells, respectively, were quantified using SYBR Green-based real-time PCR. Their associations with changes in visual analogue scale (VAS) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and percentages of CD4+ and CD8+ T cells were analyzed.
Curcumin administration significantly reduced T-bet gene expression compared to baseline and showed a positive correlation with the frequency of CD8+ T cells, while GATA3 expression remained unchanged.
These findings may provide a novel molecular perspective on curcumin's potential to influence CD8+ T cell dynamics by modulating TH1-associated transcriptional programs.
1. Courties A, Kouki I, Soliman N, Mathieu S, Sellam J. Osteoarthritis year in review 2024: Epidemiology and therapy. Osteoarthritis Cartilage. 2024;32(11):1397–404.
2. Jang S, Lee K, Ju JH. Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee. Int J Mol Sci. 2021;22(5):2619.
3. Primorac D, Molnar V, Rod E, Jeleč Ž, Čukelj F, Matišić V, et al. Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations. Genes (Basel). 2020;11(8):854.
4. Demehri S, Kasaeian A, Roemer FW, Guermazi A. Osteoarthritis year in review 2022: imaging. Osteoarthritis Cartilage. 2023;31(8):1003–11.
5. Dong Y, Yan Y, Zhou J, Zhou Q, Wei H. Evidence on risk factors for knee osteoarthritis in middle-older aged: a systematic review and meta analysis. J Orthop Surg Res. 2023;18(1):634.
6. Li YS, Luo W, Zhu SA, Lei GH. T Cells in Osteoarthritis: Alterations and Beyond. Front Immunol. 2017;8:356.
7. Wen Z, Qiu L, Ye Z, Tan X, Xu X, Lu M, et al. The role of Th/Treg immune cells in osteoarthritis. Front Immunol. 2024;15:1393418.
8. Zou Y, Liu C, Wang Z, Li G, Xiao J. Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies. Journal of Orthopaedic Translation. 2024;48:123–32.
9. Chow YY, Chin KY. The Role of Inflammation in the Pathogenesis of Osteoarthritis. Mediators Inflamm. 2020;2020:8293921.
10. Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. Jama. 2021;325(6):568–78.
11. Richard MJ, Driban JB, McAlindon TE. Pharmaceutical treatment of osteoarthritis. Osteoarthritis Cartilage. 2023;31(4):458–66.
12. Fang S, Zhang B, Xiang W, Zheng L, Wang X, Li S, et al. Natural products in osteoarthritis treatment: bridging basic research to clinical applications. Chin Med. 2024;19(1):25.
13. Lee YT, Yunus MHM, Ugusman A, Yazid MD. Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis. Antioxidants (Basel). 2022;11(9):1852.
14. Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohajeri SA, Ghoryani M, Mohammadi M. Immunoregulatory Effects of Krocina™, a Herbal Medicine Made of Crocin, on Osteoarthritis Patients: A Successful Clinical Trial in Iran. Iran J Allergy Asthma Immunol. 2020;19(3):253–63.
15. Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017;6(10):92.
16. Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, et al. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. Molecules. 2022;27(14):4400.
17. Dehzad MJ, Ghalandari H, Nouri M, Askarpour M. Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Cytokine. 2023;164:156144.
18. Peng Y, Ao M, Dong B, Jiang Y, Yu L, Chen Z, et al. Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures. Drug Des Devel Ther. 2021;15:4503–25.
19. Atabaki M, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran. Int Immunopharmacol. 2020;85:106607.
20. Evans CM, Jenner RG. Transcription factor interplay in T helper cell differentiation. Brief Funct Genomics. 2013;12(6):499–511.
21. Marks KE, Rao DA. T peripheral helper cells in autoimmune diseases. Immunol Rev. 2022;307(1):191–202.
22. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74(1):5–17.
23. Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. Int J Mol Sci. 2019;20(23):6008.
24. Kopitar-Jerala N. The Role of Interferons in Inflammation and Inflammasome Activation. Front Immunol. 2017;8:873.
25. Nees TA, Rosshirt N, Zhang JA, Platzer H, Sorbi R, Tripel E, et al. T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability. J Clin Med. 2020;9(8):2423.
26. Kanakasabai S, Casalini E, Walline CC, Mo C, Chearwae W, Bright JJ. Differential regulation of CD4(+) T helper cell responses by curcumin in experimental autoimmune encephalomyelitis. J Nutr Biochem. 2012;23(11):1498–507.
27. Castro CN, Barcala Tabarrozzi AE, Winnewisser J, Gimeno ML, Antunica Noguerol M, Liberman AC, et al. Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes. Clin Exp Immunol. 2014;177(1):149–60.
28. Khosropour S, Shahvarooghi E, Rezaeizadeh H, Esmaeelzadeh M. Curcumin and Its Semisynthetic Derivative F-Curcumin Ameliorate the Expression of Cytokines in Autoimmune Encephalomyelitis Mouse Models of Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2023;22(6):575–87.
29. Dong C, Fu T, Ji J, Li Z, Gu Z. The role of interleukin-4 in rheumatic diseases. Clin Exp Pharmacol Physiol. 2018;45(8):747–54.
30. Chong L, Zhang W, Nie Y, Yu G, Liu L, Lin L, et al. Protective effect of curcumin on acute airway inflammation of allergic asthma in mice through Notch1-GATA3 signaling pathway. Inflammation. 2014;37(5):1476-85.
31. Antunes DM, Rodrigues M, Guimarães DM, Duarte CME, Miguita L, Corrêa L, et al. Nonsteroidal Anti-inflammatory Drugs Modulate Gene Expression of Inflammatory Mediators in Oral Squamous Cell Carcinoma. Anticancer Res. 2019;39(5):2385–94.
32. Cho JY. Immunomodulatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) at the clinically available doses. Arch Pharm Res. 2007;30(1):64–74.
33. Pemmari A, Tuure L, Hämäläinen M, Leppänen T, Moilanen T, Moilanen E. Effects of ibuprofen on gene expression in chondrocytes from patients with osteoarthritis as determined by RNA-Seq. RMD Open. 2021;7(3):e001846.
34. Singh KP, Miaskowski C, Dhruva AA, Flowers E, Kober KM. Mechanisms and Measurement of Changes in Gene Expression. Biol Res Nurs. 2018;20(4):369–82.
35. Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016;17(10):1712.
36. Corley M, Burns MC, Yeo GW. How RNA-Binding Proteins Interact with RNA: Molecules and Mechanisms. Mol Cell. 2020;78(1):9-29.
37. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018;9:402.
38. Turner M, Díaz-Muñoz MD. RNA-binding proteins control gene expression and cell fate in the immune system. Nat Immunol. 2018;19(2):120–9.
39. Hosokawa H, Rothenberg EV. How transcription factors drive choice of the T cell fate. Nat Rev Immunol. 2021;21(3):162–76.
40. Luckheeram RV, Zhou R, Verma AD, Xia B. CD4⁺T cells: differentiation and functions. Clin Dev Immunol. 2012;2012:925135.
2. Jang S, Lee K, Ju JH. Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee. Int J Mol Sci. 2021;22(5):2619.
3. Primorac D, Molnar V, Rod E, Jeleč Ž, Čukelj F, Matišić V, et al. Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations. Genes (Basel). 2020;11(8):854.
4. Demehri S, Kasaeian A, Roemer FW, Guermazi A. Osteoarthritis year in review 2022: imaging. Osteoarthritis Cartilage. 2023;31(8):1003–11.
5. Dong Y, Yan Y, Zhou J, Zhou Q, Wei H. Evidence on risk factors for knee osteoarthritis in middle-older aged: a systematic review and meta analysis. J Orthop Surg Res. 2023;18(1):634.
6. Li YS, Luo W, Zhu SA, Lei GH. T Cells in Osteoarthritis: Alterations and Beyond. Front Immunol. 2017;8:356.
7. Wen Z, Qiu L, Ye Z, Tan X, Xu X, Lu M, et al. The role of Th/Treg immune cells in osteoarthritis. Front Immunol. 2024;15:1393418.
8. Zou Y, Liu C, Wang Z, Li G, Xiao J. Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies. Journal of Orthopaedic Translation. 2024;48:123–32.
9. Chow YY, Chin KY. The Role of Inflammation in the Pathogenesis of Osteoarthritis. Mediators Inflamm. 2020;2020:8293921.
10. Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. Jama. 2021;325(6):568–78.
11. Richard MJ, Driban JB, McAlindon TE. Pharmaceutical treatment of osteoarthritis. Osteoarthritis Cartilage. 2023;31(4):458–66.
12. Fang S, Zhang B, Xiang W, Zheng L, Wang X, Li S, et al. Natural products in osteoarthritis treatment: bridging basic research to clinical applications. Chin Med. 2024;19(1):25.
13. Lee YT, Yunus MHM, Ugusman A, Yazid MD. Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis. Antioxidants (Basel). 2022;11(9):1852.
14. Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohajeri SA, Ghoryani M, Mohammadi M. Immunoregulatory Effects of Krocina™, a Herbal Medicine Made of Crocin, on Osteoarthritis Patients: A Successful Clinical Trial in Iran. Iran J Allergy Asthma Immunol. 2020;19(3):253–63.
15. Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017;6(10):92.
16. Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, et al. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. Molecules. 2022;27(14):4400.
17. Dehzad MJ, Ghalandari H, Nouri M, Askarpour M. Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Cytokine. 2023;164:156144.
18. Peng Y, Ao M, Dong B, Jiang Y, Yu L, Chen Z, et al. Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures. Drug Des Devel Ther. 2021;15:4503–25.
19. Atabaki M, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran. Int Immunopharmacol. 2020;85:106607.
20. Evans CM, Jenner RG. Transcription factor interplay in T helper cell differentiation. Brief Funct Genomics. 2013;12(6):499–511.
21. Marks KE, Rao DA. T peripheral helper cells in autoimmune diseases. Immunol Rev. 2022;307(1):191–202.
22. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74(1):5–17.
23. Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. Int J Mol Sci. 2019;20(23):6008.
24. Kopitar-Jerala N. The Role of Interferons in Inflammation and Inflammasome Activation. Front Immunol. 2017;8:873.
25. Nees TA, Rosshirt N, Zhang JA, Platzer H, Sorbi R, Tripel E, et al. T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability. J Clin Med. 2020;9(8):2423.
26. Kanakasabai S, Casalini E, Walline CC, Mo C, Chearwae W, Bright JJ. Differential regulation of CD4(+) T helper cell responses by curcumin in experimental autoimmune encephalomyelitis. J Nutr Biochem. 2012;23(11):1498–507.
27. Castro CN, Barcala Tabarrozzi AE, Winnewisser J, Gimeno ML, Antunica Noguerol M, Liberman AC, et al. Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes. Clin Exp Immunol. 2014;177(1):149–60.
28. Khosropour S, Shahvarooghi E, Rezaeizadeh H, Esmaeelzadeh M. Curcumin and Its Semisynthetic Derivative F-Curcumin Ameliorate the Expression of Cytokines in Autoimmune Encephalomyelitis Mouse Models of Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2023;22(6):575–87.
29. Dong C, Fu T, Ji J, Li Z, Gu Z. The role of interleukin-4 in rheumatic diseases. Clin Exp Pharmacol Physiol. 2018;45(8):747–54.
30. Chong L, Zhang W, Nie Y, Yu G, Liu L, Lin L, et al. Protective effect of curcumin on acute airway inflammation of allergic asthma in mice through Notch1-GATA3 signaling pathway. Inflammation. 2014;37(5):1476-85.
31. Antunes DM, Rodrigues M, Guimarães DM, Duarte CME, Miguita L, Corrêa L, et al. Nonsteroidal Anti-inflammatory Drugs Modulate Gene Expression of Inflammatory Mediators in Oral Squamous Cell Carcinoma. Anticancer Res. 2019;39(5):2385–94.
32. Cho JY. Immunomodulatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) at the clinically available doses. Arch Pharm Res. 2007;30(1):64–74.
33. Pemmari A, Tuure L, Hämäläinen M, Leppänen T, Moilanen T, Moilanen E. Effects of ibuprofen on gene expression in chondrocytes from patients with osteoarthritis as determined by RNA-Seq. RMD Open. 2021;7(3):e001846.
34. Singh KP, Miaskowski C, Dhruva AA, Flowers E, Kober KM. Mechanisms and Measurement of Changes in Gene Expression. Biol Res Nurs. 2018;20(4):369–82.
35. Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016;17(10):1712.
36. Corley M, Burns MC, Yeo GW. How RNA-Binding Proteins Interact with RNA: Molecules and Mechanisms. Mol Cell. 2020;78(1):9-29.
37. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018;9:402.
38. Turner M, Díaz-Muñoz MD. RNA-binding proteins control gene expression and cell fate in the immune system. Nat Immunol. 2018;19(2):120–9.
39. Hosokawa H, Rothenberg EV. How transcription factors drive choice of the T cell fate. Nat Rev Immunol. 2021;21(3):162–76.
40. Luckheeram RV, Zhou R, Verma AD, Xia B. CD4⁺T cells: differentiation and functions. Clin Dev Immunol. 2012;2012:925135.
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| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| CD4-positive T-lymphocytes CD8-positive T-lymphocyte Curcumin GATA3 transcription factor Knee Osteoarthritis T-bet protein | ||
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How to Cite
1.
Ghoryani M, Gorgani S, Atabaki M, Noori E, Shariati-Sarabi Z, Mohammadi M. Curcumin-mediated Modulation of T-bet and CD8+ T Cells: A Potential Anti-inflammatory Mechanism in Knee Osteoarthritis. Iran J Allergy Asthma Immunol. 2026;:1-10.
