Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts

-

English
12 pages
Obtenez un accès à la bibliothèque pour le consulter en ligne
En savoir plus

Description

Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL-1) on the expression of cathepsins K and L which have been implicated in matrix degradation, TGF-β1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGF-β1. HFL-1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGF-β1. Results Collagen deposition in lungs was decreased by 17-28% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%-39%) and K (41%-76%) and a 30% decrease in TGF-β1 expression. Moreover, Tunel staining of lung tissue revealed a 33-41% increase in apoptotic cells after curcumin treatment. These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-β1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion This study demonstrates that curcumin increases the expression of cathepsins K and L in lung which an effect on lung fibroblast cell behavior such as proliferation, migration and apoptosis rates and on the expression of TGF-β1 in mouse lung and HFL-1 cells. These results suggest that cathepsin-inducing drugs such as curcumin may be beneficial in the treatment of lung fibrosis.

Sujets

Informations

Publié par
Publié le 01 janvier 2011
Nombre de lectures 13
Langue English
Poids de l'ouvrage 2 Mo
Signaler un problème
Zhanget al.Respiratory Research2011,12:154 http://respiratoryresearch.com/content/12/1/154
R E S E A R C HOpen Access Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts 1 1,22 12 2 Dongwei Zhang , Chuangfang Huang, Changfu Yang , Renzuo J Liu , Jifeng Wang , Jianzhao Niuand 1* Dieter Brömme
Abstract Background:Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycininduced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods:We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL1) on the expression of cathepsins K and L which have been implicated in matrix degradation, TGFb1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGFb1. HFL1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGFb1. Results:Collagen deposition in lungs was decreased by 1728% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%39%) and K (41%76%) and a 30% decrease in TGFb1 expression. Moreover, Tunel staining of lung tissue revealed a 3341% increase in apoptotic cells after curcumin treatment. Thesein vivodata correlated well with data obtained from the human fibroblast line, HFL1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGFb1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion:This study demonstrates that curcumin increases the expression of cathepsins K and L in lung which an effect on lung fibroblast cell behavior such as proliferation, migration and apoptosis rates and on the expression of TGFb1 in mouse lung and HFL1 cells. These results suggest that cathepsininducing drugs such as curcumin may be beneficial in the treatment of lung fibrosis. Keywords:lung fibrosis, curcumin, cathepsins, collagen, TGFβ1, apoptosis, protease inhibitors.
Background Lung fibrosis is accompanied by fibroblast proliferation and excessive extracellular matrix deposition primarily in the form of collagens. This leads to a progressive loss of lung function and ultimately death. Besides anti
* Correspondence: dbromme@interchange.ubc.ca 1 Department of Oral and Biological Science, Faculty of Dentistry, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada Full list of author information is available at the end of the article
inflammatory drugs, there is presently no effective and approved medication available in western countries. However, curcumin, an antioxidant from the spice tur meric, is used as alternative medicine in India and China for various inflammatory conditions and lung related ailments and the NIH is presently funding sev eral clinical studies to evaluate the efficacy of curcumin http://clinicaltrials.gov/ct2/results?term=curcumin. Smith and coworkers, have recently demonstrated that
© 2011 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.