(5R)-5-hydroxytriptolide (LLDT-8) protects against bleomycin-induced lung fibrosis in mice

Acta Pharmacologica Sinica

Volumn 28, Issue 4, 2007, Pages 518-525

  Ren, Yong Xin ^a   Zhou, Ru ^a   Tang, Wei ^a   Wang, Wen Hai ^a   Li, Yuan Chao ^a   Yang, Yi Fu ^a   Zuo, Jian Ping ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

(5R) 5 hydroxytriptolide; Bleomycin; Cytokines; Lung fibrosis

Indexed keywords

5 HYDROXYTRIPTOLIDE; BLEOMYCIN; CYTOKINE; INTERLEUKIN 4; MALONALDEHYDE; SUPEROXIDE DISMUTASE; TRANSFORMING GROWTH FACTOR ALPHA; TRIPTOLIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CYTOKINE PRODUCTION; DRUG EFFECT; DRUG INHIBITION; ENZYME ACTIVITY; FEMALE; LEUKOCYTE DIFFERENTIAL COUNT; LUNG FIBROSIS; LUNG HOMOGENATE; LUNG LAVAGE; LYMPHOCYTE; MACROPHAGE; MOUSE; NEUTROPHIL; NONHUMAN; WEIGHT REDUCTION;

ANIMALS; ANTIMETABOLITES; BLEOMYCIN; BRONCHOALVEOLAR LAVAGE FLUID; CYTOKINES; DITERPENES; FEMALE; LUNG; MICE; MICE, INBRED C57BL; PROTECTIVE AGENTS; PULMONARY FIBROSIS; SUPEROXIDE DISMUTASE;

EID: 33947693204     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1111/j.1745-7254.2007.00524.x     Document Type: Article

References (37)

1. Gharaee-Kermani M, Phan SH. Molecular mechanisms of and possible treatment strategies for idiopathic pulmonary fibrosis. Curr Pharm Des 2005; 11: 3943-71.
2. Khalil N, O'Connor R. Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment. Can Med Assoc J 2004; 171: 153-60.
3. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001; 345: 517-25.
4. Ozyurt H, Sogut S, Yildirim Z, Kart L, Iraz M, Armutcu F, et al. Inhibitory effect of caffeic acid phenethyl ester on bleomycin-induced lung fibrosis in rats. Clin Chim Acta 2004; 339: 65-75.
5. Asano K, Matsuishi J, Yu Y, Kasahara T, Hisamitsu T. Suppressive effects of Tripterygium wilfordii Hook f., a traditional Chinese medicine, on collagen arthritis in mice. Immunopharmacology 1998; 39: 117-26.
6. Gu WZ, Banerjee S, Rauch J, Brandwein SR. Suppression of renal disease and arthritis, and prolongation of survival in MRL-lpr mice treated with an extract of Tripterygium wilfordii Hook f. Arthritis Rheum 1992; 35: 1381-6.
7. Gu WZ, Brandwein SR. Inhibition of type II collagen-induced arthritis in rats by triptolide. Int J Immunopharmacol 1998; 20: 389-400.
8. Tao X, Davis LS, Hashimoto K, Lipsky PE. The Chinese herbal remedy, T2, inhibits mitogen-induced cytokine gene transcription by T cells, but not initial signal transduction. J Pharmacol Exp Ther 1996; 276: 316-25.
9. Chen BJ. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk Lymphoma 2001; 42: 253-65.
10. Huynh PN, Hikim AP, Wang C, Stefonovic K, Lue YH, Leung A, et al. Long-term effects of triptolide on spermatogenesis, epididymal sperm function, and fertility in male rats. J Androl 2000; 21: 689-99.
11. Zhou R, Zhang F, He PL, Zhou WL, Wu QL, Xu JY, et al. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo. Int Immunopharmacol 2005; 5: 1895-903.
12. Zhou R, Tang W, Ren YX, He PL, Zhang F, Shi LP, et al. (5R)-5-hydroxytriptolide attenuated collagen-induced arthritis in DBA/1 mice via suppressing interferon-gamma production and its related signaling. J Pharmacol Exp Ther 2006b; 318: 35-44.
13. Tang W, Yang Y, Zhang F, Li YC, Zhou R, Wang JX, et al. Prevention of graft-versus-host disease by a novel immuno-suppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells. Int Immunopharmacol 2005; 5: 1904-13.
14. Tang W, Zhou R, Yang Y, Li YC, Yang YF, Zuo JP. Suppression of (5R)-5-hydroxytriptolide (LLDT-8) on allograft rejection in full MHC-mismatched mouse cardiac transplantation. Transplantation 2006; 81: 927-33.
15. Zhou R, Tang W, Ren YX, He PL, Yang YF, Li YC, et al. Preventive effects of (5R)-5-hydroxytriptolide on concanavalin A-induced hepatitis. Eur J Pharmacol 2006a; 537: 181-9.
16. 6 Kremer S, Brever R, Lossos IS. Effect of immunomodulators on bleomycin-induced lung injury. Respiration 1999; 66: 455-62.
17. + T cell function. Jpn J Cancer Res 1993; 84: 315-25.
18. Borzone G, Moreno R, Urrea R, Meneses M, Oyarzun M. Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001; 163: 1648-53.
19. Tarnell EB, Oliver BL, Johnson GM, Watts FL, Thrall, RS. Superoxide anion production by rat neutrophils at various stages of bleomycin-induced lung injury. Lung 1992; 170: 41-50.
20. Oury TD, Thakker K, Menache M, Chang LY, Crapo JD, Day BJ. Attenuation of bleomycin-induced pulmonary fibrosis by a catalytic antioxidant metalloporphyrin. Am J Respir Crit Care Med 2001; 164: 164-9.
21. Kinnula VL, Fattman CL, Tan RJ, Oury TD. Oxidative stress in pulmonary fibrosis. Am J Respir Crit Care Med 2005; 172: 417-22.
22. Kuwanl K, Nakashima N, Inoshima I, Hagimoto N, Fujita M, Yoshimi M, et al. Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias. Lab Invest 2002; 82: 1695-706.
23. Bellocq A, Azoulay C, Marullo S, Flahault A, Fouqueray B, Philippe C, et al. Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta 1 release from human epithelial alveolar cells through two different mechanisms. Am J Respir Cell Mol Biol 1999; 21: 128-36.
24. Salvemini D, Riley DP, Cuzzocrea S. SOD mimetics are coming of age. Nat Rev Drug Discov 2002; 1: 367-74.
25. Piguet PF, Ribaux C, Karpuz V, Grau GE, Kapanci Y. Expression and localization of tumor necrosis factor-alpha and its mRNA in idiopathic pulmonary fibrosis. Am J Pathol 1993; 143: 651-5.
26. Yara S, Kawakami K, Kudeken N, Tohyama M, Teruya K, Chinen T, et al. FTS reduced bleomycin-induced cytokine and chemokine production and inhibits pulmonary fibrosis in mice. Clin Exp Immunol 2001; 124: 77-85.
27. Walter N, Collard HR, King TE Jr. Current perspectives on the treatment of idiopathic pulmonar fibrosis. Proc Am Thorac Soc 2006; 3: 330-8.
28. Izbicki G, Segel MJ, Christensen TG, Conner MW, Breuer R. Time course of bleomycin-induced lung fibrosis. Int J Exp Path 2002; 83: 111-9.
29. Gharaee-Kermani M, Phan SH. Role of cytokines and cytokine therapy in wound healing and fibrotic diseases. Curr Pharm Des 2001; 11: 1083-103.
30. Lossos IS, Or R, Goldstein RH, Conner MW, Breuer R. Amelioration of bleomycin-induced pulmonary injury by cyclosporin A. Exp Lung Res 1996; 22: 337-49.
31. Zhu J, Cohen DA, Goud SN, Kaplan AM. Contribution of T lymphocytes to the development of bleomycin-induced pulmonary fibrosis. Ann NY Acad Sci 1996; 796: 194-202.
32. Sharma SK, MacLean JA, Pinto C, Kradin RL. The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury. Am J Respir Crit Care Med 1996; 154: 193-200.
33. Huaux F, Liu T, McGarry B, Ullenbruch M, Phan SH. Dual roles of IL-4 in lung injury and fibrosis. J Immunol 2003; 170: 2083-92.
34. Arai T, Abe K, Matsuoka H, Yoshida M, Mori M, Goya S, et al. Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo. Am J Physiol Lung Cell Mol Physiol 2000; 278: L914-22.
35. Sakamoto H, Zhao LH, Jain F, Kradin R. IL-12p40(-/-) mice treated with intratracheal bleomycin exhibit decreased pulmonary inflammation and increased fibrosis. Exp Mol Pathol 2002; 72: 1-9.
36. Gharaee-Kermani M, Nozaki Y, Hatano K, Phan SH. Lung interleukin-4 gene expression in a murine model of bleomycin-induced pulmonary fibrosis. Cytokine 2001; 15: 138-47.
37. Krishna G, Liu K, Shigemitsu H, Gao M, Raffin TA, Rosen GD. PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis. Am J Pathol 2001; 158: 997-1004.