© 1999 American Heart Association, Inc.
Vascular Biology |
9-cis Retinoic Acid Induces Monocyte Chemoattractant Protein-1 Secretion in Human Monocytic THP-1 Cells
From the Department of Vascular and Cardiac Diseases (L.Z., C.L.B., R.S.N.), Parke-Davis Pharmaceutical Research, Ann Arbor, Mich, and The Lipid Research Laboratory (M.A.), Technion Faculty of Medicine, Rambam Medical Center and the Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel.
Abstract—Monocyte migration and
activation are regulated by monocyte chemoattractant protein-1 (MCP-1).
Prior studies have shown MCP-1 expression is modulated by a variety of
ligands that act through extracellular receptors. In the current study,
we show 9-cis retinoic acid (RA), a ligand for the nuclear hormone
receptor retinoid X receptor (RXR) and retinoic acid receptor (RAR),
markedly induces the expression of MCP-1. In human THP-1 monocytic
leukemia cells cultured with RA (0.05 to 500 nmol/L), MCP-1 expression
was induced rapidly, significantly, and dose-dependently by as much as
165-fold. MCP-1 RNA level was also increased in RA-treated cells.
Expression of PPAR
, a heterodimer partner of RXR, is also
markedly induced by RA in THP-1 cells. However, BRL49653, a PPAR
ligand, failed to induce MCP-1 secretion either alone or to modify the
expression level induced by RA. In contrast, BRL49653 significantly
increased MCP-1 (biotinylated MCP-1) binding to THP-1 cells, whereas RA
had no effect. Other peroxisome proliferator activated receptor
(PPAR) ligands, 15d-PGJ2 and troglitazone (PPAR),
Wy14,643 (PPAR
), and PD195599 (PPARß) inhibited the induction of
MCP-1 by RA. RA's effect on MCP-1 expression in human elutriated
monocytes were similar to that observed in the THP-1 cells. These
studies identify RA as a nuclear signal for MCP-1 induction in
undifferentiated human monocytic cells. These studies also suggest
monocyte MCP-1 expression induced through RA may modulate cell
migration.
Key Words: PPAR • MCP-1 • nuclear hormone receptor • monocyte migration • CCR2 • ELISA • RNase protection assay
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