help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on January 14, 2005, doi:10.1165/rcmb.2004-0288OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0288OCv1
32/4/342    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Sullivan, D. E.
Right arrow Articles by Brody, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sullivan, D. E.
Right arrow Articles by Brody, A. R.
American Journal of Respiratory Cell and Molecular Biology. Vol. 32, pp. 342-349, 2005
© 2005 American Thoracic Society
DOI: 10.1165/rcmb.2004-0288OC

Tumor Necrosis Factor-{alpha} Induces Transforming Growth Factor-ß1 Expression in Lung Fibroblasts Through the Extracellular Signal–Regulated Kinase Pathway

Deborah E. Sullivan, MaryBeth Ferris, Derek Pociask and Arnold R. Brody

Department of Pathology and Laboratory Medicine and the Lung Biology Program, Tulane University Health Sciences Center, New Orleans, Louisiana

Correspondence and requests for reprints should be addressed to Deborah E. Sullivan, Ph.D., Department of Pathology and Laboratory Medicine SL-79, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112. E-mail: dsulliva{at}tulane.edu

Increased expression of transforming growth factor (TGF)-ß1 and tumor necrosis factor (TNF)-{alpha} are thought to play important roles in the development of pulmonary fibrosis. We recently reported that TNF-{alpha} upregulates TGF-ß1 expression in primary mouse lung fibroblasts (MLFs), a key cell population in fibrogenesis. In the present study, we have investigated signal transduction pathways involved in TNF-{alpha} upregulation of TGF-ß1 in both primary MLFs and the Swiss 3T3 fibroblast cell line. Treatment of fibroblasts with TNF-{alpha} resulted in a significant increase in TGF-ß1 protein as measured by ELISA. The increase in protein was preceded by a 200–400% increase in TGF-ß1 mRNA detected by quantitative, real-time, reverse transcriptase–polymerase chain reaction. Western blot analysis showed that TNF-{alpha} activated the extracellular signal–regulated kinase (ERK), and inhibitors of the ERK-specific mitogen-activated protein kinase pathway (PD98059 or U0126) blocked TNF-{alpha} induction of TGF-ß1 mRNA and protein. mRNA stability experiments showed that TNF-{alpha} increased the half-life of TGF-ß1 mRNA to more than 24 h compared with ~ 15 h in unstimulated cells. Expression of constitutively active MEK1 that selectively phosphorylates ERK was sufficient for TGF-ß1 mRNA stabilization in Swiss 3T3 fibroblasts. These results indicate that TNF-{alpha} activates the ERK-specific mitogen-activated protein kinase pathway leading to increased TGF-ß1 production in fibroblasts, primarily via a post-transcriptional mechanism that involves stabilization of the TGF-ß1 transcript.

Key Words: lung fibroblasts • transforming growth factor-ß1 • tumor neurosis factor-{alpha} • extracellular signal-regulated kinase




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. B. Manning, T. Sabo-Attwood, R. F. Robledo, M. B. MacPherson, M. Rincon, P. Vacek, D. Hemenway, D. J. Taatjes, P. J. Lee, and B. T. Mossman
Targeting the MEK1 Cascade in Lung Epithelium Inhibits Proliferation and Fibrogenesis by Asbestos
Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 618 - 626.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Tabata, R. Tabata, Y. Kadokawa, S. Hisamori, M. Takahashi, M. Mishima, T. Nakano, and H. Kubo
Thalidomide Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice
J. Immunol., July 1, 2007; 179(1): 708 - 714.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. R. Wilson, M. E. Goddard, K. P. O'Dea, S. Choudhury, and M. Takata
Differential roles of p55 and p75 tumor necrosis factor receptors on stretch-induced pulmonary edema in mice
Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L60 - L68.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. Tabata, Y. Kadokawa, R. Tabata, M. Takahashi, K. Okoshi, Y. Sakai, M. Mishima, and H. Kubo
All-trans-Retinoic Acid Prevents Radiation- or Bleomycin-induced Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., December 15, 2006; 174(12): 1352 - 1360.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Esnault, Z.-J. Shen, E. Whitesel, and J. S. Malter
The Peptidyl-Prolyl Isomerase Pin1 Regulates Granulocyte-Macrophage Colony-Stimulating Factor mRNA Stability in T Lymphocytes
J. Immunol., November 15, 2006; 177(10): 6999 - 7006.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Wang, J. Zhang, S. Theel, J. J. Barb, P. J. Munson, and R. L. Danner
Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements
Nucleic Acids Res., June 6, 2006; 34(10): 3044 - 3056.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. A. Derbigny, M. S. Kerr, and R. M. Johnson
Pattern Recognition Molecules Activated by Chlamydia muridarum Infection of Cloned Murine Oviduct Epithelial Cell Lines
J. Immunol., November 1, 2005; 175(9): 6065 - 6075.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society.