INTERLEUKIN-4 INDUCES EXPRESSION OF THE INTEGRIN ALPHA(V)BETA(3) VIA TRANSACTIVATION OF THE BETA(3) GENE

Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin alpha(v) beta(3), whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on gp, expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing beta(3) mRNA levels by a mechanism involving transactivation of the beta(3), gene. Moreover, IL-4 augmented beta(3) mRNA is mirrored by plasma membrane appearance of alpha(v) beta(3). As IL-4 induces beta(3) and not alpha(v) mRNA, the beta(3) chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced alpha v beta 3, is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of EMMs with the cytokine enhances alpha(v) beta(3)- mediated binding to vitronectin 5-fold, Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests alpha(v) beta(3), may play a role in the inflammatory response of macrophages.