| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and Smad3 Signaling Link Inflammation to Chronic Fibrogenesis1
* Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada;
Service de Pneumologie et Réanimation Respiratoire, Centre Hospitalier Universitaire du Bocage et Université de Bourgogne, Dijon, France;
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada
Transient adenovirus-mediated gene transfer of IL-1
(AdIL-1), a proinflammatory cytokine, induces marked inflammation and severe and progressive fibrosis in rat lungs. This is associated with an increase in TGF-1 concentration in bronchoalveolar lavage (BAL) fluid. TGF-1 is a key cytokine in the process of fibrogenesis, using intracellular signaling pathways involving Smad2 and Smad3. In this study we investigate whether inflammation induced by IL-1 is able to independently induce lung fibrosis in mice deficient in the Smad3 gene. Seven days after AdIL-1 administration, similar levels of IL-1 transgene are seen in BAL in both wild-type (WT) and knockout (KO) mice, and BAL cell profiles demonstrated a similar marked neutrophilic inflammation. Phospho-Smad2 staining was positive in areas of inflammation in both WT and KO mice at day 7. By day 35 after transient IL-1 expression, WT mice showed marked fibrosis in peribronchial areas, quantified by picrosirius red staining and morphometry. However, there was no evidence of fibrosis or collagen accumulation in IL-1-treated KO mice, and peribronchial areas were not different from KO mice treated with the control adenovector. TGF-1 and phospho-Smad2 were strongly positive at day 35 in fibrotic areas observed in WT mice, but no such staining was detectable in KO mice. The IL-1-induced chronic fibrotic response in mouse lungs is dependent on Smad3. KO and WT animals demonstrated a similar inflammatory response to overexpression of IL-1 indicating that inflammation must link to the Smad3 pathway, likely through TGF-, to induce progressive fibrosis.
This article has been cited by other articles:
|
|
 |
|
  T. E. Downing, T. A. Sporn, R. R. Bollinger, R. D. Davis, W. Parker, and S. S. Lin Pulmonary Histopathology in an Experimental Model of Chronic Aspiration Is Independent of Acidity Experimental Biology and Medicine, October 1, 2008; 233(10): 1202 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yu, G. C. Sharp, and H. Braley-Mullen TGF-{beta} Promotes Thyroid Epithelial Cell Hyperplasia and Fibrosis in IFN-{gamma}-Deficient NOD.H-2h4 Mice J. Immunol., August 1, 2008; 181(3): 2238 - 2245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Vidal, A. L. Serrano, M. Tjwa, M. Suelves, E. Ardite, R. De Mori, B. Baeza-Raja, M. Martinez de Lagran, P. Lafuste, V. Ruiz-Bonilla, et al. Fibrinogen drives dystrophic muscle fibrosis via a TGF{beta}/alternative macrophage activation pathway Genes & Dev., July 1, 2008; 22(13): 1747 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Haydont, B. L. Riser, J. Aigueperse, and M.-C. Vozenin-Brotons Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-{beta}1 Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1332 - C1341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Black Jr. and P. C. Trackman Transforming Growth Factor-{beta}1 (TGF{beta}1) Stimulates Connective Tissue Growth Factor (CCN2/CTGF) Expression in Human Gingival Fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent Mechanism: STATINS WITH FORSKOLIN BLOCK TGF{beta}1-INDUCED CCN2/CTGF EXPRESSION J. Biol. Chem., April 18, 2008; 283(16): 10835 - 10847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Ganter, J. Roux, B. Miyazawa, M. Howard, J. A. Frank, G. Su, D. Sheppard, S. M. Violette, P. H. Weinreb, G. S. Horan, et al. Interleukin-1{beta} Causes Acute Lung Injury via {alpha}v{beta}5 and {alpha}v{beta}6 Integrin-Dependent Mechanisms Circ. Res., April 11, 2008; 102(7): 804 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Moore and C. M. Hogaboam Murine models of pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L152 - L160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Decologne, M. Kolb, P. J. Margetts, F. Menetrier, Y. Artur, C. Garrido, J. Gauldie, P. Camus, and P. Bonniaud TGF-beta1 Induces Progressive Pleural Scarring and Subpleural Fibrosis J. Immunol., November 1, 2007; 179(9): 6043 - 6051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamada, K. Kuwano, T. Maeyama, M. Yoshimi, N. Hamada, J. Fukumoto, K. Egashira, K. Hiasa, K. Takayama, and Y. Nakanishi Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis J. Clin. Pathol., August 1, 2007; 60(8): 916 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pochetuhen, I. G. Luzina, V. Lockatell, J. Choi, N. W. Todd, and S. P. Atamas Complex Regulation of Pulmonary Inflammation and Fibrosis by CCL18 Am. J. Pathol., August 1, 2007; 171(2): 428 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Young, R. Pasula, P. M. Gulleman, G. H. Deutsch, and F. X. McCormack Susceptibility of Hermansky-Pudlak Mice to Bleomycin-Induced Type II Cell Apoptosis and Fibrosis Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 67 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Black Jr., A. H. Palamakumbura, M. Stan, and P. C. Trackman Tissue-specific Mechanisms for CCN2/CTGF Persistence in Fibrotic Gingiva: INTERACTIONS BETWEEN cAMP AND MAPK SIGNALING PATHWAYS, AND PROSTAGLANDIN E2-EP3 RECEPTOR MEDIATED ACTIVATION OF THE c-JUN N-TERMINAL KINASE J. Biol. Chem., May 25, 2007; 282(21): 15416 - 15429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gauldie, M. Kolb, K. Ask, G. Martin, P. Bonniaud, and D. Warburton Smad3 Signaling Involved in Pulmonary Fibrosis and Emphysema Proceedings of the ATS, November 1, 2006; 3(8): 696 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Martinez and M. P. Keane Update in diffuse parenchymal lung diseases 2005. Am. J. Respir. Crit. Care Med., May 15, 2006; 173(10): 1066 - 1071. [Full Text] [PDF]
|
|
|
|
|
|
L. R. Young, M. T. Borchers, H. L. Allen, R. S. Gibbons, and F. X. McCormack Lung-Restricted Macrophage Activation in the Pearl Mouse Model of Hermansky-Pudlak Syndrome J. Immunol., April 1, 2006; 176(7): 4361 - 4368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ask, G. E. M. Martin, M. Kolb, and J. Gauldie Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls. Proceedings of the ATS, January 1, 2006; 3(4): 389 - 393. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
