9-cis retinoic acid induces monocyte chemoattractant protein-1 secretion in human monocytic THP-1 cells.
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 PPARgamma, a heterodimer partner of RXR, is also markedly induced by RA in THP-1 cells. However, BRL49653, a PPARgamma 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-PGJ(2) and troglitazone (PPARgamma), Wy14,643 (PPARalpha), and PD195599 (PPARbeta) 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.
Zhu
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Department of Vascular and Cardiac Diseases Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan, USA.
Bisgaier
C L
CL
Aviram
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M
Newton
R S
RS
D000077556:Alitretinoin; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000077556:Alitretinoin; D014212:Tretinoin