help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhou, Z.
Right arrow Articles by Morse, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, Z.
Right arrow Articles by Morse, D.
(American Journal of Pathology. 2005;166:27-37.)
© 2005 American Society for Investigative Pathology

Carbon Monoxide Suppresses Bleomycin-Induced Lung Fibrosis

Zhihong Zhou*, Ruiping Song*, Cheryl L. Fattman{ddagger}, Sara Greenhill*, Sean Alber{dagger}, Tim D. Oury{ddagger}, Augustine M.K. Choi* and Danielle Morse*

From the Division of Pulmonary, Allergy, and Critical Care Medicine,* and the Departments of Cell Biology and Physiology{dagger} and Pathology,{ddagger} University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Idiopathic pulmonary fibrosis is an incurable fibrosing disorder that progresses relentlessly to respiratory failure. We hypothesized that a product of heme oxygenase activity, carbon monoxide (CO), may have anti-fibrotic effects. To test this hypothesis, mice treated with intratracheal bleomycin were exposed to low-concentration inhaled CO or ambient air. Lungs of mice treated with CO had significantly lower hydroxyproline accumulation than controls. Fibroblast proliferation, thought to play a central role in the progression of fibrosis, was suppressed by in vitro exposure to CO. CO caused increased cellular levels of p21Cip1 and decreased levels of cyclins A and D. This effect was independent of the observed suppression of MAPK’s phosphorylation by CO but was dependent on increased cGMP levels. Further, CO-exposed cells elaborated significantly less fibronectin and collagen-1 than control cells. This same effect was seen in vivo. Suppression of collagen-1 production did not depend on MAPK or guanylate cyclase signaling pathways but did depend on the transcriptional regulator Id1. Taken together, these data suggest that CO exerts an anti-fibrotic effect in the lung, and this effect may be due to suppression of fibroblast proliferation and/or suppression of matrix deposition by fibroblasts.




This article has been cited by other articles:


Home page
 Eur Respir JHome page
Q. Ye, Y. Dalavanga, N. Poulakis, S. U. Sixt, J. Guzman, and U. Costabel
Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis
Eur. Respir. J., May 1, 2008; 31(5): 1030 - 1036.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. Wang, J.-Y. S. Lee, J. H. Kwak, Y. He, S. I. Kim, and M. E. Choi
Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction
Am J Physiol Renal Physiol, March 1, 2008; 294(3): F508 - F517.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. Traylor, T. Hock, and N. Hill-Kapturczak
Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-beta1 in renal epithelial cells
Am J Physiol Renal Physiol, September 1, 2007; 293(3): F885 - F894.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. E. Fredenburgh, M. A. Perrella, and S. A. Mitsialis
The Role of Heme Oxygenase-1 in Pulmonary Disease
Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 158 - 165.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. W. Ryter, D. Morse, and A. M. K. Choi
Carbon Monoxide and Bilirubin: Potential Therapies for Pulmonary/Vascular Injury and Disease
Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 175 - 182.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
X. M. Wang, Y. Zhang, H. P. Kim, Z. Zhou, C. A. Feghali-Bostwick, F. Liu, E. Ifedigbo, X. Xu, T. D. Oury, N. Kaminski, et al.
Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis
J. Exp. Med., December 25, 2006; 203(13): 2895 - 2906.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Nakao, J. Schmidt, T. Harada, A. Tsung, B. Stoffels, R. J. Cruz Jr., J. Kohmoto, X. Peng, K. Tomiyama, N. Murase, et al.
A Single Intraperitoneal Dose of Carbon Monoxide-Saturated Ringer's Lactate Solution Ameliorates Postoperative Ileus in Mice
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1265 - 1275.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
X. Zhang, P. Shan, G. Jiang, S. S-M. Zhang, L. E. Otterbein, X.-Y. Fu, and P. J. Lee
Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury
FASEB J, October 1, 2006; 20(12): 2156 - 2158.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. W. Ryter, J. Alam, and A. M. K. Choi
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Physiol Rev, April 1, 2006; 86(2): 583 - 650.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
Y. Jin and A. M. K. Choi
Cytoprotection of Heme Oxygenase-1/Carbon Monoxide in Lung Injury
Proceedings of the ATS, October 1, 2005; 2(3): 232 - 235.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. Morse and A. M. K. Choi
Heme Oxygenase-1: From Bench to Bedside
Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 660 - 670.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.