Differential effects of 9-cis retinoic acid on expression of CC chemokine receptors in human monocytes.
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 6h after a 100nM 9-CRA treatment and reached a maximal level at 12h. 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 Ca(2+) concentration and the chemotactic activity increased in 9-CRA-treated cells in response to the CCR1-dependent chemokines Lkn-1, MIP-1alpha, and RANTES, and the CCR2-specific chemokine MCP-1. Increased surface expression of CCR1 and the Ca(2+) 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.
Department of Clinical Laboratory Science, School of Medicine, Eulji University, Daejun 301-832, South Korea.
In Sik
IS
Kim
Yoon Suk
YS
Kim
Sung-Wuk
SW
Jang
Ho Joong
HJ
Sung
Ki Hoon
KH
Han
Doe Sun
DS
Na
Jesang
J
Ko
D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; C515300:CCR1 protein, human; C515334:CCR2 protein, human; D018925:Chemokines; D012333:RNA, Messenger; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D000077556:Alitretinoin; D014212:Tretinoin; D002118:Calcium