|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine, National Cardiovascular Center, Suita, Osaka, Japan
* To whom correspondence should be addressed. E-mail: nnagaya{at}ri.ncvc.go.jp.
C-type natriuretic peptide (CNP) has been shown to play an important role in the regulation of vascular tone and remodeling. However, the physiological role of CNP in the lung remains unknown. Accordingly, we investigated whether CNP infusion attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. After intratracheal injection of BLM or saline, mice were randomized to receive continuous infusion of CNP or vehicle for 14 days. CNP infusion significantly reduced the total number of cells and the numbers of macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF). Interestingly, CNP markedly reduced BALF IL-1
level. Immunohistochemical analysis demonstrated that CNP significantly inhibited infiltration of macrophages into the alveolar and interstitial regions. CNP infusion significantly attenuated BLM-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. CNP markedly decreased the number of Ki-67-positive cells in fibrotic lesions of the lung, suggesting anti-proliferative effects of CNP on pulmonary fibrosis. Kaplan-Meier survival curves demonstrated that BLM mice treated with CNP had a significantly higher survival rate than those given vehicle. These results suggest that continuous infusion of CNP attenuates BLM-induced pulmonary fibrosis and improves survival in BLM mice, at least in part by inhibition of pulmonary inflammation and cell proliferation.
This article has been cited by other articles:
![]() |
A. R. Hemnes, A. Zaiman, and H. C. Champion PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Murakami, N. Nagaya, T. Itoh, M. Kataoka, T. Iwase, T. Horio, Y. Miyahara, Y. Sakai, K. Kangawa, and H. Kimura Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L59 - L65. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nakatani-Okuda, H. Ueda, S.-i. Kashiwamura, A. Sekiyama, A. Kubota, Y. Fujita, S. Adachi, Y. Tsuji, T. Tanizawa, and H. Okamura Protection against bleomycin-induced lung injury by IL-18 in mice Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L280 - L287. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |