A Significant Increase in the Gene Expression of GATA-3 Following the Treatment of Osteoarthritis Patients with Crocin
Abstract
Osteoarthritis (OA) is known to be the most prevalent form of joint disease. We conducted this clinical trial to investigate the effects of KrocinaTM, a natural product containing crocin, on the gene expression of unique transcription factors of various T cell subsets in patients with OA.
We collected 40 peripheral blood samples of OA patients receiving Krocina™ and equal number of those who took a placebo (IRCT2015021910507N2, NCT03375814). RNA extraction was performed from the cultured peripheral blood mononuclear cells of the OA patients who received Krocina™ and placebo and SYBR Green Real-time PCR technique was applied to assess the relative gene expression of T-bet, GATA3, ROR-γt, and FOXP3 as the unique transcription factors of various T cell subsets.
The relative gene expression of T-bet and ROR-γt insignificantly decreased in the Krocina™ receiving group as compared to the placebo group. In addition, the relative gene expressions of GATA-3 and FOXP3 after the treatment with KrocinaTM showed a significant and insignificant increase, respectively. Moreover, an insignificant decrease was observed in the gene expression of GATA-3 and FOXP3 in the placebo group. A significant and insignificant decrease in the gene expression of T-bet and ROR- γt was detected in the OA patients who received a placebo. GATA-3 is known as a unique transcription factor for the differentiation of T-cells to the Th2 subset.
The significant increase in the gene expression of GATA-3 in the patients with OA treated with crocin may suggest the beneficial effect of crocin on shifting towards the Th2 subset and enhancing an anti-inflammatory condition.
1. Ding Q, Zhong H, Qi Y, Cheng Y, Li W, Yan S, Wang X.. Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model. Inflammation Research. 2013;62(1):17–25. https://doi.org/10.1007/s00011-012-0546-3.
2. Hochberg MC. Opportunities for the prevention of osteoarthritis. In Seminars in Arthritis and Rheumatism. 2010;39(5):321–2. https://doi.org/10.1016/j.semarthrit.2010.02.001.
3. Singh Y, Khan SA, Owais M, Abbas M, Parvez A, Kamal A. Th1/Th2 profile in patients suffering with osteoarthritis and rheumatoid arthritis: An analytical observational study. CHRISMED J Heal Res. 2014;1(4):258. https://doi.org/10.4103/2348-3334.142998.
4. Niu X, He D, Zhang X, Yue T, Li N, Zhang JZ, Dong C, Chen G. IL-21 regulates Th17 cells in rheumatoid arthritis. Hum Immunol. 2010;71(4):334–41.
5. Bani S, Pandey A, Agnihotri VK, Pathania V, Singh B. Selective Th2 upregulation by Crocus sativus: a neutraceutical spice. Evidence-Based Complementary and Alternative Medicine. 2011:1-9.
6. Adali F, Gonul Y, Aldemir M, Hazman O, Ahsen A, Bozkurt MF, Sen OG, Keles I, Keles H. Investigation of the effect of crocin pretreatment on renal injury induced by infrarenal aortic occlusion. J Surg Res. 2016;203(1):145-53. https://doi.org/10.1016/j.jss.2016.03.022.
7. Li L, Zhang H, Jin S, Liu C. Effects of crocin on inflammatory activities in human fibroblast-like synoviocytes and collagen-induced arthritis in mice. Immunol Res. 2018;66(3):406–13 https://doi.org/10.1007/s12026-018-8999-2.
8. Park JH, Lee KY, Park B, Yoon J. Suppression of T h2 chemokines by crocin via blocking of ERK‐MAPK/NF‐κ B/STAT 1 signalling pathways in TNF-α/IFN-γ stimulated human epidermal keratinocytes. Exp Dermatol. 2015;24(8):634-6. https://doi.org/10.1111/exd.12726.
9. Kanhere A, Hertweck A, Bhatia U, Gökmen MR, Perucha E, Jackson I, Lord GM, Jenner RG. T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements. Nat Commun. 2012;3(1):1-2. https://doi.org/10.1038/ncomms2260.
10. Faedo A, Ficara F, Ghiani M, Aiuti A, Rubenstein JL, Bulfone A. Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis. Mech Dev. 2002;116(1–2):157–60. https://doi.org/10.1016/S0925-4773(02)00114-4.
11. Zheng WP, Flavell RA.The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89(4):587–96. https://doi.org/10.1016/S0092-8674(00)80240-8.
12. Zhang DH, Cohn L, Ray P, Bottomly K, Ray A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem. 1997;272(34):21597-603. https://doi.org/10.1074/jbc.272.34.21597.
13. Nalbant A, Eskier D. Genes associated with T helper 17 cell differentiation and function. Front Biosci. 2016;8(3):427–35. https://doi.org/10.2741/e777.
14. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126(6):1121-33. https://doi.org/10.1016/j.cell.2006.07.035.
15. Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, O’Malley JT, Kapur R, Levy DE, Kansas GS, Kaplan MH. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol. 2007;178(8):4901–7. https://doi.org/10.4049/jimmunol.178.8.4901.
16. Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS. T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα
and RORγ. Immunity. 2008;28(1):29–39. https://doi.org/10.1016/j.immuni.2007.11.016.
17. Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2011;241(1):260-8. https://doi.org/10.1111/j.1600-065X.2011.01018.x.
18. 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. https://doi.org/10.18502/ijaai.v19i3.3453.
19. Szabo SJ, Dighe AS, Gubler U, Murphy KM. Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med. 1997;185(5):817-24. https://doi.org/10.1084/jem.185.5.817.
20. Glimcher LH, Murphy KM. Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 2000;14(14):1693–711. https://doi.org/https://10.1101/gad.14.14.1693.
21. Zhou C, Bai W, Chen Q, Xu Z, Zhu X, Wen A, Yang X. Protective effect of crocetin against burn-induced intestinal injury. J Surg Res. 2015;198(1):99–107. https://doi.org/10.1016/j.jss.2015.05.052.
22. Wampold BE, Minami T, Tierney SC, Baskin TW, Bhati KS. The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials. J Clin Psychol. 2005;61(7):835–54. https://doi.org/10.1002/jclp.20129.
23. Hwang ES, Szabo SJ, Schwartzberg PL, Glimcher LH. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science. 2005;307(5708):430-3. https://doi.org/10.1126/science.1103336.
24. Stockinger B, Veldhoen M, Martin B. Th17 T cells: linking innate and adaptive immunity. InSeminars Immunol. 2007;9(6):353-361. https://doi.org/10.1016/j.smim.2007.10.008.
25. Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, Takaesu G, Hori S, Yoshimura A, Kobayashi T. Foxp3 Inhibits RORγt-mediated IL-17A mRNA Transcription through Direct Interaction with RORγt. J Biol Chem. 2008;283(25):17003–8. https://doi.org/10.1074/jbc.M801286200.
26. McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM, Burgeon E, Lane WS, Lambert JN, Curran T, Verdine GL.Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science. 1993;262(5134):750–4. https://doi.org/10.1126/science.8235597.
27. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5(6):472–84. https://doi.org/10.1038/nri1632.
28. Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR. NF-AT components define a family of transcription factors targeted in T-cell activation. Nature. 1994;369(6480):497-502. https://doi.org/10.1038/369497a0.
29. López-Rodríguez C, Aramburu J, Rakeman AS, Rao A. NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Proc Natl Acad Sci. 1999;96(13):7214–9.
30. Hoey T, Sun YL, Williamson K, Xu X. Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity. 1995;2(5):461–72. https://doi.org/10.1016/1074-7613(95)90027-6.
31. Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without. J Immunol. 191(12):5785–91. https://doi.org/10.4049/jimmunol.1390055.
32. Bettelli E, Dastrange M, Oukka M. Foxp3 interacts with nuclear factor of activated T cells and NF-κB to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci. 2005;102(14):5138–43. https://doi.org/10.1073/pnas.0501675102.
33. Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, Mathis D. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006;126(2):375-87. https://doi.org/10.1016/j.cell.2006.05.042.
34. Macian F, López-Rodríguez C, Rao A. Partners in transcription: NFAT and AP-1. Oncogene. 2001;20(19):2476-89.
35. Hermann-Kleiter N, Baier G. NFAT pulls the strings during CD4+ T helper cell effector functions. Blood, J Am Soc Hematol. 2010;115(15):2989–97. https://doi.org/10.1182/blood-2009-10-233585.
36. Hu H, Djuretic I, Sundrud MS, Rao A.Transcriptional partners in regulatory T cells: Foxp3, Runx and NFAT. Trends Immunol. 2007;28(8):329–32. https://doi.org/10.1016/j.it.2007.06.006.
37. Kim B, Park B. Saffron carotenoids inhibit STAT3 activation and promote apoptotic progression in IL-6-stimulated liver cancer cells. Oncol Rep. 2018;39(4):1883–91. https://doi.org/10.3892/or.2018.6232.
38. Zhang L, Li JM, Liu XG, Ma DX, Hu NW, Li YG, Li W, Hu Y, Yu S, Qu X, Yang MX. Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J Clin Immunol. 2011;31(4):606-14. https://doi.org/10.1007/s10875-011-9540-8.
39. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61. https://doi.org/10.1126/science.1079490.
40. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330-6. https://doi.org/10.1038/ni904.
41. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+ CD25+ T regulatory cells.
Nat Immunol. 2003;4(4):337-42. https://doi.org/doi:10.1038/ni909.
42. Mantel PY, Kuipers H, Boyman O, Rhyner C, Ouaked N, Rückert B, Karagiannidis C, Lambrecht BN, Hendriks RW, Crameri R, Akdis CA. GATA3-driven TH2 responses inhibit TGF-β1–induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol. 2007;5(12):e329. https://doi.org/10.1371/journal.pbio.0050329.
43. Guo SY, Ding YJ, Li L, Zhang T, Zhang ZZ, Zhang ES. Correlation of CD. Genet Mol Res. 2015;14(3):7290–6. https://doi.org/10.4238/2015.July.3.4.
44. Sun H, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, Shen H. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 2008;133(3):415-26. https://doi.org/10.1016/j.cell.2008.03.026.
45. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem. 2007;282(13):9358-63. https://doi.org/10.1074/jbc.C600321200.
46. Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. Immunity. 2009;30(1):80–91. https://doi.org/10.1016/j.immuni.2008.11.010.
47. Raghavan S, Cao D, Widhe M, Roth K, Herrath J, Engström M, Roncador G, Banham AH, Trollmo C, Catrina AI, Malmström V. FOXP3 expression in blood, synovial fluid and synovial tissue during inflammatory arthritis and intra-articular corticosteroid treatment. Ann Rheum Dis. 2009;68(12):1908-15. https://doi.org/10.1136/ard.2008.100768.
48. Li S, Liu X, Lei J, Yang J, Tian P, Gao Y. Crocin protects podocytes against oxidative stress and inflammation induced by high glucose through inhibition of NF-κB. Cell Physiol Biochem. 2017;42(4):1481–92. https://doi.org/10.1159/000479212.
2. Hochberg MC. Opportunities for the prevention of osteoarthritis. In Seminars in Arthritis and Rheumatism. 2010;39(5):321–2. https://doi.org/10.1016/j.semarthrit.2010.02.001.
3. Singh Y, Khan SA, Owais M, Abbas M, Parvez A, Kamal A. Th1/Th2 profile in patients suffering with osteoarthritis and rheumatoid arthritis: An analytical observational study. CHRISMED J Heal Res. 2014;1(4):258. https://doi.org/10.4103/2348-3334.142998.
4. Niu X, He D, Zhang X, Yue T, Li N, Zhang JZ, Dong C, Chen G. IL-21 regulates Th17 cells in rheumatoid arthritis. Hum Immunol. 2010;71(4):334–41.
5. Bani S, Pandey A, Agnihotri VK, Pathania V, Singh B. Selective Th2 upregulation by Crocus sativus: a neutraceutical spice. Evidence-Based Complementary and Alternative Medicine. 2011:1-9.
6. Adali F, Gonul Y, Aldemir M, Hazman O, Ahsen A, Bozkurt MF, Sen OG, Keles I, Keles H. Investigation of the effect of crocin pretreatment on renal injury induced by infrarenal aortic occlusion. J Surg Res. 2016;203(1):145-53. https://doi.org/10.1016/j.jss.2016.03.022.
7. Li L, Zhang H, Jin S, Liu C. Effects of crocin on inflammatory activities in human fibroblast-like synoviocytes and collagen-induced arthritis in mice. Immunol Res. 2018;66(3):406–13 https://doi.org/10.1007/s12026-018-8999-2.
8. Park JH, Lee KY, Park B, Yoon J. Suppression of T h2 chemokines by crocin via blocking of ERK‐MAPK/NF‐κ B/STAT 1 signalling pathways in TNF-α/IFN-γ stimulated human epidermal keratinocytes. Exp Dermatol. 2015;24(8):634-6. https://doi.org/10.1111/exd.12726.
9. Kanhere A, Hertweck A, Bhatia U, Gökmen MR, Perucha E, Jackson I, Lord GM, Jenner RG. T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements. Nat Commun. 2012;3(1):1-2. https://doi.org/10.1038/ncomms2260.
10. Faedo A, Ficara F, Ghiani M, Aiuti A, Rubenstein JL, Bulfone A. Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis. Mech Dev. 2002;116(1–2):157–60. https://doi.org/10.1016/S0925-4773(02)00114-4.
11. Zheng WP, Flavell RA.The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89(4):587–96. https://doi.org/10.1016/S0092-8674(00)80240-8.
12. Zhang DH, Cohn L, Ray P, Bottomly K, Ray A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem. 1997;272(34):21597-603. https://doi.org/10.1074/jbc.272.34.21597.
13. Nalbant A, Eskier D. Genes associated with T helper 17 cell differentiation and function. Front Biosci. 2016;8(3):427–35. https://doi.org/10.2741/e777.
14. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126(6):1121-33. https://doi.org/10.1016/j.cell.2006.07.035.
15. Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, O’Malley JT, Kapur R, Levy DE, Kansas GS, Kaplan MH. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol. 2007;178(8):4901–7. https://doi.org/10.4049/jimmunol.178.8.4901.
16. Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS. T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα
and RORγ. Immunity. 2008;28(1):29–39. https://doi.org/10.1016/j.immuni.2007.11.016.
17. Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2011;241(1):260-8. https://doi.org/10.1111/j.1600-065X.2011.01018.x.
18. 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. https://doi.org/10.18502/ijaai.v19i3.3453.
19. Szabo SJ, Dighe AS, Gubler U, Murphy KM. Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med. 1997;185(5):817-24. https://doi.org/10.1084/jem.185.5.817.
20. Glimcher LH, Murphy KM. Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 2000;14(14):1693–711. https://doi.org/https://10.1101/gad.14.14.1693.
21. Zhou C, Bai W, Chen Q, Xu Z, Zhu X, Wen A, Yang X. Protective effect of crocetin against burn-induced intestinal injury. J Surg Res. 2015;198(1):99–107. https://doi.org/10.1016/j.jss.2015.05.052.
22. Wampold BE, Minami T, Tierney SC, Baskin TW, Bhati KS. The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials. J Clin Psychol. 2005;61(7):835–54. https://doi.org/10.1002/jclp.20129.
23. Hwang ES, Szabo SJ, Schwartzberg PL, Glimcher LH. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science. 2005;307(5708):430-3. https://doi.org/10.1126/science.1103336.
24. Stockinger B, Veldhoen M, Martin B. Th17 T cells: linking innate and adaptive immunity. InSeminars Immunol. 2007;9(6):353-361. https://doi.org/10.1016/j.smim.2007.10.008.
25. Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, Takaesu G, Hori S, Yoshimura A, Kobayashi T. Foxp3 Inhibits RORγt-mediated IL-17A mRNA Transcription through Direct Interaction with RORγt. J Biol Chem. 2008;283(25):17003–8. https://doi.org/10.1074/jbc.M801286200.
26. McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM, Burgeon E, Lane WS, Lambert JN, Curran T, Verdine GL.Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science. 1993;262(5134):750–4. https://doi.org/10.1126/science.8235597.
27. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5(6):472–84. https://doi.org/10.1038/nri1632.
28. Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR. NF-AT components define a family of transcription factors targeted in T-cell activation. Nature. 1994;369(6480):497-502. https://doi.org/10.1038/369497a0.
29. López-Rodríguez C, Aramburu J, Rakeman AS, Rao A. NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Proc Natl Acad Sci. 1999;96(13):7214–9.
30. Hoey T, Sun YL, Williamson K, Xu X. Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity. 1995;2(5):461–72. https://doi.org/10.1016/1074-7613(95)90027-6.
31. Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without. J Immunol. 191(12):5785–91. https://doi.org/10.4049/jimmunol.1390055.
32. Bettelli E, Dastrange M, Oukka M. Foxp3 interacts with nuclear factor of activated T cells and NF-κB to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci. 2005;102(14):5138–43. https://doi.org/10.1073/pnas.0501675102.
33. Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, Mathis D. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006;126(2):375-87. https://doi.org/10.1016/j.cell.2006.05.042.
34. Macian F, López-Rodríguez C, Rao A. Partners in transcription: NFAT and AP-1. Oncogene. 2001;20(19):2476-89.
35. Hermann-Kleiter N, Baier G. NFAT pulls the strings during CD4+ T helper cell effector functions. Blood, J Am Soc Hematol. 2010;115(15):2989–97. https://doi.org/10.1182/blood-2009-10-233585.
36. Hu H, Djuretic I, Sundrud MS, Rao A.Transcriptional partners in regulatory T cells: Foxp3, Runx and NFAT. Trends Immunol. 2007;28(8):329–32. https://doi.org/10.1016/j.it.2007.06.006.
37. Kim B, Park B. Saffron carotenoids inhibit STAT3 activation and promote apoptotic progression in IL-6-stimulated liver cancer cells. Oncol Rep. 2018;39(4):1883–91. https://doi.org/10.3892/or.2018.6232.
38. Zhang L, Li JM, Liu XG, Ma DX, Hu NW, Li YG, Li W, Hu Y, Yu S, Qu X, Yang MX. Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J Clin Immunol. 2011;31(4):606-14. https://doi.org/10.1007/s10875-011-9540-8.
39. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61. https://doi.org/10.1126/science.1079490.
40. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330-6. https://doi.org/10.1038/ni904.
41. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+ CD25+ T regulatory cells.
Nat Immunol. 2003;4(4):337-42. https://doi.org/doi:10.1038/ni909.
42. Mantel PY, Kuipers H, Boyman O, Rhyner C, Ouaked N, Rückert B, Karagiannidis C, Lambrecht BN, Hendriks RW, Crameri R, Akdis CA. GATA3-driven TH2 responses inhibit TGF-β1–induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol. 2007;5(12):e329. https://doi.org/10.1371/journal.pbio.0050329.
43. Guo SY, Ding YJ, Li L, Zhang T, Zhang ZZ, Zhang ES. Correlation of CD. Genet Mol Res. 2015;14(3):7290–6. https://doi.org/10.4238/2015.July.3.4.
44. Sun H, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, Shen H. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 2008;133(3):415-26. https://doi.org/10.1016/j.cell.2008.03.026.
45. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem. 2007;282(13):9358-63. https://doi.org/10.1074/jbc.C600321200.
46. Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. Immunity. 2009;30(1):80–91. https://doi.org/10.1016/j.immuni.2008.11.010.
47. Raghavan S, Cao D, Widhe M, Roth K, Herrath J, Engström M, Roncador G, Banham AH, Trollmo C, Catrina AI, Malmström V. FOXP3 expression in blood, synovial fluid and synovial tissue during inflammatory arthritis and intra-articular corticosteroid treatment. Ann Rheum Dis. 2009;68(12):1908-15. https://doi.org/10.1136/ard.2008.100768.
48. Li S, Liu X, Lei J, Yang J, Tian P, Gao Y. Crocin protects podocytes against oxidative stress and inflammation induced by high glucose through inhibition of NF-κB. Cell Physiol Biochem. 2017;42(4):1481–92. https://doi.org/10.1159/000479212.
| Files | ||
| Issue | Vol 21 No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i1.8611 | |
| Keywords | ||
| Crocin Crocus Gene expression Osteoarthritis Transcription factors | ||
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How to Cite
1.
Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. A Significant Increase in the Gene Expression of GATA-3 Following the Treatment of Osteoarthritis Patients with Crocin. Iran J Allergy Asthma Immunol. 2022;21(1):35-43.
