PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis

被引：73

作者：

Krishna, G ^{[1
]}

Liu, KL ^{[1
]}

Shigemitsu, H ^{[1
]}

Gao, MX ^{[1
]}

Raffin, TA ^{[1
]}

Rosen, GD ^{[1
]}

机构：

[1] Stanford Univ, Med Ctr, Div Pulm & Crit Care Med, Stanford, CA 94305 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2001年 / 158卷 / 03期

关键词：

D O I：

10.1016/S0002-9440(10)64046-1

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

In this study we evaluate the antifibrotic properties of PG-490-88, a water-soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse model and found that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or 5 days after bleomycin. PG490-88 also markedly reduced the number of myofibroblasts in the bleomycin treatment group. An enzyme-linked immunosorbent assay of transforming growth factor (TGF)-beta in the bronchoalveolar lavage fluid showed a significant decrease in TGF-beta in the PG490-88-treated groups compared to the bleomycin-treated group. Additionally, triptolide blocked bleomycin-induced increase in TGF-beta mRNA in cultured normal human lung fibroblasts. The efficacy of PG490-88 when administered late after bleomycin installation suggests a potential role in the treatment of idiopathic pulmonary fibrosis.

引用

页码：997 / 1004

页数：8

共 28 条

[1] SIMPLE METHOD OF ESTIMATING SEVERITY OF PULMONARY FIBROSIS ON A NUMERICAL SCALE [J].

ASHCROFT, T ;

SIMPSON, JM ;

TIMBRELL, V .

JOURNAL OF CLINICAL PATHOLOGY, 1988, 41 (04) :467-470

[2] EXPRESSION AND SECRETION OF TYPE-BETA TRANSFORMING GROWTH-FACTOR BY ACTIVATED HUMAN MACROPHAGES [J].

ASSOIAN, RK ;

FLEURDELYS, BE ;

STEVENSON, HC ;

MILLER, PJ ;

MADTES, DK ;

RAINES, EW ;

ROSS, R ;

SPORN, MB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (17) :6020-6024

[3] BLEOMYCIN REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA IN RAT LUNG FIBROBLASTS [J].

BREEN, E ;

SHULL, S ;

BURNE, S ;

ABSHER, M ;

KELLEY, J ;

PHAN, S ;

CUTRONEO, KR .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1992, 6 (02) :146-152

[4] Pulmonary fibrosis: cytokines in the balance [J].

Coker, RK ;

Laurent, GJ .

EUROPEAN RESPIRATORY JOURNAL, 1998, 11 (06) :1218-1221

[5]

CROUCH E, 1990, AM J PHYSIOL, V259, P159

[6] Colchicine versus prednisone as treatment of usual interstitial pneumonia [J].

Douglas, WW ;

Ryu, JH ;

Bjoraker, JA ;

Schroeder, DR ;

Myers, JL ;

Tazelaar, HD ;

Swensen, SJ ;

Scanlon, PD ;

Peters, SG ;

DeRemee, RA .

MAYO CLINIC PROCEEDINGS, 1997, 72 (03) :201-209

[7]

IGNOTZ RA, 1986, J BIOL CHEM, V261, P4337

[8] RANDOMIZED CONTROLLED TRIAL COMPARING PREDNISOLONE ALONE WITH CYCLOPHOSPHAMIDE AND LOW-DOSE PREDNISOLONE IN COMBINATION IN CRYPTOGENIC FIBROSING ALVEOLITIS [J].

JOHNSON, MA ;

KWAN, S ;

SNELL, NJC ;

NUNN, AJ ;

DARBYSHIRE, JH ;

TURNERWARWICK, M .

THORAX, 1989, 44 (04) :280-288

[9] Idiopathic pulmonary fibrosis - Clinical relevance of pathologic classification [J].

Katzenstein, ALA ;

Myers, JL .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1998, 157 (04) :1301-1315

[10]

KING SL, 1994, J BIOL CHEM, V269, P13156

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