The Journal of Experimental Medicine
for flow cytometry > invitrogen
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 17 September 2001. doi:10.1084/jem.194.6.809
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 612K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, C. G.
Right arrow Articles by Elias, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, C. G.
Right arrow Articles by Elias, J. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2001/9/809/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 6, September 17, 2001 809-822

Original Article

Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1

Chun Geun Leea, Robert J. Homerb,c, Zhou Zhua, Sophie Lanonea, Xiaoman Wanga, Victor Kotelianskyd, J. Michael Shipleye, Philip Gotwalsd, Paul Noblea, Qingsheng Chena, Robert M. Seniore, and Jack A. Eliasa

a Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine
b Department of Pathology, New Haven, CT 06520
c Pathology and Laboratory Medicine Service, VA-CT Health Care System, West Haven, CT 06516
d Biogen, Inc., Cambridge, MA 02142
e Washington University School of Medicine, Section of Pulmonary and Critical Care Medicine, Barnes-Jewish Hospital, St. Louis, MO 63110
Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, Dept. of Internal Medicine, 333 Cedar St. - 105 LCI, New Haven, CT 06520-8057.203-785-3826203-785-4163

jack.elias{at}yale.edu

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-β. To test this hypothesis we compared the regulation of TGF-β in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-β1 production in transgenic animals and macrophages were the major site of TGF-β1 production and deposition in these tissues. IL-13 also activated TGF-β1 in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-β–binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-β1 activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13–induced fibrosis was also significantly ameliorated by treatment with the TGF-β antagonist soluble TGFβR-Fc (sTGFβR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-β1 in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9–dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-β pathway.

Key Words: lung • plasmin • matrix metalloproteinase-9 • CD44 • asthma

Abbreviations used in this paper: BAL, bronchoalveolar lavage; IPF, idiopathic pulmonary fibrosis; ISH, in situ hybridization; LAP, latency-associated peptide; LTBP, latent TGF-β–binding protein; MMP, matrix metalloproteinase; PAI, plasminogen activator inhibitor; RT, reverse transcription; s, soluble; uPA, urokinase type plasminogen activator; WT, wild-type.

© 2001 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS