Differential effects of 9-cis retinoic acid on expression of CC chemokine receptors in human monocytes

In Sik Kim, Yoon Suk Kim, Sung Wuk Jang, Ho Joong Sung, Ki Hoon Han, Doe Sun Na, Jesang Ko

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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 languageEnglish
Pages (from-to)611-620
Number of pages10
JournalBiochemical Pharmacology
Issue number4
Publication statusPublished - 2004 Aug 15
Externally publishedYes


  • Chemokine
  • Chemokine receptor
  • Chemotaxis
  • Inflammation
  • Monocyte
  • Retinoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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