Abstract
9-cis Retinoic acid (9-CRA) is a lipophilic molecule that binds to the retinoid X receptor (RXR). Although retinoic acid (RA) has been known to regulate neutrophil differentiation, a specific role for 9-CRA in chemokine-mediated cellular processes remains obscure. We investigated the effects of 9-CRA on expression of CC chemokine receptors (CCRs) in human monocytic THP-1 cells and peripheral blood monocytes. RNase protection assay was performed to examine the mRNA levels of CCRs in 9-CRA-treated THP-1 cells. mRNA expression of CCR1 and CCR2 was induced in both a dose and time dependent manner. CCR1 and CCR2 mRNA expression began to increase from 6 h after a 100 nM 9-CRA treatment and reached a maximal level at 12 h. Surface expression of CCRs was monitored by flow cytometry. CCR1 and CCR2 surface expression increased in 9-CRA-treated THP-1 cells, but not in untreated cells. Calcium mobilization and chemotactic activity were determined to examine the effect of 9-CRA on cell movement. The intracellular Ca2+ concentration and the chemotactic activity increased in 9-CRA-treated cells in response to the CCR1-dependent chemokines Lkn-1, MIP-1α, and RANTES, and the CCR2-specific chemokine MCP-1. Increased surface expression of CCR1 and the Ca2+ influx due to 9-CRA were confirmed in peripheral blood monocytes. Taken together, 9-CRA increases the expression levels of mRNA and protein of both CCR1 and CCR2, and the cell migration ability in THP-1 cells and peripheral blood monocytes, indicating that 9-CRA may regulate inflammatory processes through an increased response to CCR1- and CCR2-dependent chemokines.
Original language | English |
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Pages (from-to) | 611-620 |
Number of pages | 10 |
Journal | Biochemical Pharmacology |
Volume | 68 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2004 Aug 15 |
Externally published | Yes |
Keywords
- Chemokine
- Chemokine receptor
- Chemotaxis
- Inflammation
- Monocyte
- Retinoic acid
ASJC Scopus subject areas
- Biochemistry
- Pharmacology