Phorbol ester-induced U-937 differentiation: effects on integrin alpha(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, alpha(5)beta(1), 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 alpha(5)beta(1) 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 alpha(5)- and beta(1)-subunit mRNAs and the surface expression of the protein. In U-937 cells transfected with an alpha(5) promoter-reporter gene, we found that PMA induced the transcription of the alpha(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 alpha(5)beta(1) expression may be important for regulation of monocytic cell function in lung inflammation after injury.