Phorbol ester-induced U-937 differentiation: effects on integrin α 5 gene transcription

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 α 5 promoter-reporter gene, we found that PMA induced the transcription of the α 5 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.