PLA(2)-INDEPENDENT INDUCTION OF CSF-1 GENE-EXPRESSION IN GROWTH-ARRESTED FIBROBLASTS

At the site of a wound or an infection, localized production of colony -stimulating factor-1 (CSF-1) by resident macrophages is chemotactic f or circulating monocytes. Several intracellular signaling pathways, in cluding those initiated in response to activation of phospholipase A(2 ) (PLA(2)) have been proposed to play a role in the regulation of CSF- 1 gene expression. The goal of these studies was to determine whether PLA(2) is required for the initial increase in CSF-1 gene expression i n serum-or IL-1 alpha-stimulated growth-arrested fibroblasts. IL-1 alp ha- or serum-stimulation of growth-arrested fibroblasts had no effect on PLA(2) enzyme activity and inhibitors of cytosolic or Ca2+-independ ent PLA(2) activity had no effect on IL-1 alpha- or serum-mediated inc reases in CSF-1 mRNA levels. High concentrations of the PLA(2) inhibit ors, 4-bromophenacyl lactone and quinacrine, resulted in a generalized decrease in cellular mRNA levels. Our results, obtained in fibroblast s, suggest treatment with 4-bromophenacyl lactone or quinacrine, inste ad of inhibiting PLA(2) activity specifically, results in a generalize d depression of cellular mRNA levels. These data demonstrate that the initial increase in CSF-1 gene expression in growth-arrested fibroblas ts treated with serum or IL-1 alpha occurs through a PLA(2)-independen t mechanism. (C) 1998 Elsevier Science Ireland Ltd. All rights reserve d.