Transforming growth factor-β stimulates interleukin-11 transcription via complex activating protein-1-dependent pathways

Weiliang Tang, Liu Yang, Yu Chung Yang, Sean Leng, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

Studies were undertaken to characterize the mechanism by which transforming growth factor-β1 (TGF-β1) stimulates epithelial cell interleukin (IL)-11 production. Nuclear run-on studies demonstrated that TGF- β1 is a potent stimulator of IL-11 gene transcription. TGF-β1 also stimulated the luciferase activity in cells transfected with reporter gene constructs containing nucleotides -728 to +58 of the IL-11 promoter. Studies with progressive 5' deletion constructs and site-specific mutations demonstrated that this stimulation was dependent on 2 AP-1 sites between nucleotides -100 and -82 in the IL-11 promoter. Mobility shift assays demonstrated that TGF-β1 stimulated AP-1 protein-DNA binding to both AP-1 sites. Supershift analysis demonstrated that JunD was the major moiety contributing to AP-1-DNA binding in unstimulated cells and that c-Jun-, Fra- 1-, and Fra-2-DNA binding were increased whereas JunD-DNA binding was decreased in TGF-β1-stimulated cells. The sequence in the IL-11 promoter that contains the AP-1 sites also conferred TGF-β1 responsiveness, in a position-independent fashion, on a heterologous minimal promoter. Thus, TGF- β1 stimulates IL-11 gene transcription via a complex AP-1-dependent pathway that is dependent on 2 AP-1 motifs between nucleotides -100 and -82 that function as an enhancer in the IL-11 promoter.

Original languageEnglish (US)
Pages (from-to)5506-5513
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number10
DOIs
Publication statusPublished - Mar 6 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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