Phorbol ester-induced U-937 differentiation: Effects on integrin α5 gene transcription

Bonnie K. Boles, Jeffrey Ritzenthaler, Thomas Birkenmeier, Jesse Roman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Lung injury is accompanied by increased deposition of fibronectin (FN) matrices. Activated monocytic cells recruited to sites of lung injury express integrin receptors for FN that mediate their interaction with this matrix. One such integrin, α5β1, mediates many of the biological effects of FN, and its expression may be important for immune cell function at sites of lung injury. Herein, we examine the expression of α5β1 in response to the tumor promoter phorbol 12-myristate 13-acetate (PMA) in the human promonocytic cell line U-937. We demonstrate that PMA enhanced the adherence of U-937 cells to FN by increasing the expression of both the α5- and β1- subunit mRNAs and the surface expression of the protein. In U-937 cells transfected with an α5 promoter-reporter gene, we found that PMA induced the transcription of the α5 gene by acting on very specific promoter sequences other than activator protein-1 in a protein kinase C-dependent manner. Lipopolysaccharide had a similar effect. Modulation of α5β1 expression may be important for regulation of monocytic cell function in lung inflammation after injury.

Original languageEnglish
Pages (from-to)L703-L712
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number4 22-4
StatePublished - Apr 1 2000

Keywords

  • Fibronectin
  • Phorbol 12- myristate 13-acetate
  • Promoter
  • Protein kinase C
  • Transcription factor

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