To investigate the effects of triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F (TWHF), on the co-stimulatory molecule expression and interleukin-12 (IL-12) production from THP-1 cells.
THP-1 cells were differentiated into macrophage-like cells by Me2SO, and then cultured with IFN-γ (500 kU/L) and lipopolysaccharide (LPS) (1 mg/L) with or without triptolide. The surface molecule expressions were analyzed on a FACScan flow cytometer. IL-12p40, IL-12p70 were assayed by ELISA.
Tripolide suppressed CD80 and CD86 expressions on IFN-γ (500 kU/L) and LPS (1 mg/L) activated THP-1 cells at nontoxic dosages of 2.5–0.625 μg/L. Furthermore, the production of IL-12p40 and IL-12p70 were also significantly reduced in THP-1 cells exposed to triptolide.
Triptolide impairs the antigen-presenting function by inhibiting CD80 and CD86 expressions and decreased IL-12p40 and IL-12p70 (bioactive form) productions from the activated THP-1 cells.
Schwartz RH . T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol 1985; 3: 237–61.
Greenfield EA, Nguyen KA, Kuchroo VK . CD28/B7 costimulation. Crit Rev Immunol 1998; 18: 389–418.
Salomon B, Bluestone JA . Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 2001; 19: 225–52.
Jonker M, Ossevoort And MA, Vierboom M . Blocking the CD80 and CD86 costimulation molecules: lessons to be learned from animal models. Transplantation 2002; 73: S23–6.
Anand S, Chen L . Control of autoimmune diseases by the B7-CD28 family molecules. Curr Pharm Des 2004; 10: 121–8.
Gottlieb AB, Lebwohl M, Totoritis MC, Abdulghani AA, Shuey SR, Romano P, et al. Clinical and histologic response to singledose treatment of moderate to severe psoriasis with an anti-CD80 monoclonal antibody. J Am Acad Dermatol 2002; 47: 692–700.
Tao XL, Sun Y, Dong Y, Xiao YL, Hu DW, Shi YP, et al. A prospective, controlled, double-blind, cross-over study of tripterygium wilfodii hook F in treatment of rheumatoid arthritis. Chin Med J 1989; 102: 327–32.
Lipsky PE, Tao XL . A potential new treatment for rheumatoid arthritis: thunder god vine. Semin Arthritis Rheum 1997; 26: 713–23.
Qiu D, Kao PN . Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook f. Drugs R D 2003; 4: 1–18.
Su D, Song Y, Li R . Comparative clinical study of rheumatoid arthritis treated by triptolide and an ethyl acetate extract of Tripterygium wilfordii. Chin J Integrated Trad West Med 1990; 10: 144–6.
Gu WZ, Brandwein SR . Inhibition of type II collagen-induced arthritis in rats by triptolide. Int J Immunopharmacol 1998; 20: 389–400.
Li L, Wakukami T, Teng WP, Di GX, Murakami K, Mimura G . The effect of triptolide on the development of insulitis in lowdose streptozotocin induced diabetic mice and on the beta-cells of normal mice. Chin J Diabetes 1994; 2: 69–75.
Yi ZW, Li L . Clinical study of nephrotic syndrome in children treated by triptolide. Hunan Med J 1994; 11: 284–5.
Lu H, Hachida M, Enosawa S, Li XK, Suzuki S, Koyanagi H . Immunosuppressive effect of triptolide in vitro. Transplant Proc 1999; 31: 2056–7.
Chan MA, Kohlmeier JE, Branden M, Jung M, Benedict SH . Triptolide is more effective in preventing T cell proliferation and interferon-gamma production than is FK506. Phytother Res 1999; 13: 464–7.
Yang Y, Liu Z, Tolosa E, Yang J, Li L . Triptolide induces apoptotic death of T lymphocyte. Immunopharmacology 1998; 40: 139–49.
Hong Y, Zhou W, Li K, Sacks SH . Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells. Kidney Int 2002; 62: 1291–300.
Li H, Liu ZH, Dai CS, Liu D, Li LS . Triptolide inhibits proinflammatory factor-induced over-expression of class II MHC and B7 molecules in renal tubular epithelial cells. Acta Pharmacol Sin 2002; 23: 775–81.
Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, et al. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol 1998; 16: 495–521.
Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Method 1983; 65: 55–63.
Kubin M, Chow JM, Trinchieri G . Differential regulation of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-1 beta production in human myeloid leukemia cell lines and peripheral blood mononuclear cells. Blood 1994; 83: 1847–55.
Wu Y, Wang Y, Zhong C, Li Y, Li X, Sun B . The suppressive effect of triptolide on experimental autoimmune uveoretinitis by down-regulating Th1-type response. Int Immunopharmacol 2003; 3: 1457–65.
Lin JF, Zhu H, Liu XQ, Zhen HP, Zheng YL . Triptolide prolong the survival of heart transplant in mice. Strait Pharmacentical J 1998; 10: 29–30.
Yang J, Fan Z, Dai C, Wang J, Liu Z, Li L . Antirenal allograft rejection effects of triptolide in rats. J Nephrol Dialy Trans plant 1997; 6: 214–20.
Chen BJ, Liu C, Cui X, Fidler JM, Chao NJ . Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion. Transplantation 2000; 70: 1442–7.
Du ZY, Li XY, Li YC, Wang SY . Analysis of triptolide-regulated gene expression in Jurkat cells by complementary DNA microarray. Acta Pharmacol Sin 2003; 24: 864–72.
Monteyne P, Guillaume B, Sindic CJ . B7-1 (CD80), B7-2 (CD86), interleukin-12 and transforming growth factor-beta mRNA expression in CSF and peripheral blood mononuclear cells from multiple sclerosis patients. J Neuroimmunol 1998; 91: 198–203.
Liu H, Liu ZH, Chen ZH, Yang JW, Li LS . Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes. Acta Pharmacol Sin 2000; 21: 782–6.
Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 1999; 274: 13443–50.
Caamano J, Hunter CA . NF-kappaB family of transcription factors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev 2002; 15: 414–29.
Project supported by the National Natural Science Foundation of China (No A30171086) and the Knowledge Innovation Program of the Chinese Academy of Sciences (No KSCX2-SW-202).
About this article
Toxicological Sciences (2019)
Plant Cell Reports (2015)
<i>Lactobacillus acidophilus</i> L-92 Cells Activate Expression of Immunomodulatory Genes in THP-1 Cells
Bioscience of Microbiota, Food and Health (2014)
A Pseudopterane Diterpene Isolated From the Octocoral Pseudopterogorgia acerosa Inhibits the Inflammatory Response Mediated by TLR-Ligands and TNF-Alpha in Macrophages
PLoS ONE (2013)