A Comparison of Macrophage Colony-Stimulating Factor (M-CSF) Gene Expression in Primary and Immortalized Endothelial Cells

Abstract

M-CSF is produced by a wide variety of cell types, including EC, fibroblasts, and monocyte/ macrophages, where it functions as a survival factor and a chemotactic agent for monocytes. An early event in the development of atherosclerosis is the infiltration of monocytes into the artery wall. Local expression of M-CSF by EC lining the blood vessels is thought to promote the growth and survival of lesional monocytes and macrophages, thus enhancing lesion development and disease progression. Primary cultures of EC are difficult to maintain for long periods of time, which complicates their use for biochemical and molecular analysis. As a step toward identifying a representative endothelial-like cell line, serum-dependent and IL-1-dependent changes in M-CSF gene expression in two endothelial-like cell lines were compared to that detected in primary EC cultures. The data presented here demonstrate that the two endothelial-like cell lines, like primary cultures of EC, express the M-CSF gene under basal conditions. In both types of cell cultures, IL-1 alpha stimulation increased M-CSF mRNA levels 2–7-fold, whereas serum stimulation elicited a more modest effect (2–3-fold increase). The IL-1 alpha-induced change in M-CSF gene expression is mediated at the transcriptional level, and M-CSF promoter activity is, in part, dependent on the activity of the NF kappa B-inducing kinase. Collectively, our results demonstrate that either endothelial-like cell line would be a representative model in which endothelial-specific changes in M-CSF gene expression could be identified.