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

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.