PLA2-independent induction of CSF-1 gene expression in growth-arrested fibroblasts

An Song, Xiao Ling Xia, Rafat A. Siddiqui, Maureen A. Harrington

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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-1α-stimulated growth-arrested fibroblasts. IL-1α- or serum-stimulation of growth-arrested fibroblasts had no effect on PLA2 enzyme activity and inhibitors of cytosolic or Ca2+-independent PLA2 activity had no effect on IL-1α- 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-1α occurs through a PLA2-independent mechanism.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalInternational Journal of Hematology
Volume67
Issue number3
DOIs
StatePublished - Apr 1998

Keywords

  • Arachidonic acid
  • Interleukin-1
  • Macrophages

ASJC Scopus subject areas

  • Hematology

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