PLA2-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 for circulating monocytes. Several intracellular signaling pathways, including those initiated in response to activation of phospholipase A2 (PLA2) have been proposed to play a role in the regulation of CSF-1 gene expression. The goal of these studies was to determine whether PLA2 is required for the initial increase in CSF-1 gene expression in serum- or IL-1 alpha-stimulated growth-arrested fibroblasts. IL-1 alpha- or serum-stimulation of growth-arrested fibroblasts had no effect on PLA2 enzyme activity and inhibitors of cytosolic or Ca(2+)-independent PLA2 activity had no effect on IL-1 alpha- or serum-mediated increases in CSF-1 mRNA levels. High concentrations of the PLA2 inhibitors, 4-bromophenacyl lactone and quinacrine, resulted in a generalized decrease in cellular mRNA levels. Our results, obtained in fibroblasts, suggest treatment with 4-bromophenacyl lactone or quinacrine, instead of inhibiting PLA2 activity specifically, results in a generalized depression of cellular mRNA levels. These data demonstrate that the initial increase in CSF-1 gene expression in growth-arrested fibroblasts treated with serum or IL-1 alpha occurs through a PLA2-independent mechanism.
Song
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A
Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, USA.
Xia
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XL
Siddiqui
R A
RA
Harrington
M A
MA
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D016895:Culture Media, Serum-Free; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D051379:Mice; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
D016895:Culture Media, Serum-Free; D007375:Interleukin-1; D016173:Macrophage Colony-Stimulating Factor; D010741:Phospholipases A; D054467:Phospholipases A2