Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1

Geun Lee Chun Geun Lee, R. J. Homer, Z. Zhu, S. Lanone, X. Wang, V. Koteliansky, J. M. Shipley, P. Gotwals, P. Noble, Q. Chen, R. M. Senior, J. A. Elias

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)809-821
Number of pages13
JournalJournal of Experimental Medicine
Volume194
Issue number6
DOIs
StatePublished - Sep 17 2001

Keywords

  • Asthma
  • CD44
  • Lung
  • Matrix metalloproteinase-9
  • Plasmin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β<sub>1</sub>'. Together they form a unique fingerprint.

  • Cite this

    Chun Geun Lee, G. L., Homer, R. J., Zhu, Z., Lanone, S., Wang, X., Koteliansky, V., Shipley, J. M., Gotwals, P., Noble, P., Chen, Q., Senior, R. M., & Elias, J. A. (2001). Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1. Journal of Experimental Medicine, 194(6), 809-821. https://doi.org/10.1084/jem.194.6.809