Peroxisome-proliferator-activated-receptor gamma (PPARgamma) independent induction of CD36 in THP-1 monocytes by retinoic acid.
Retinoic acid (RA) has been shown to regulate cellular growth and differentiation of a variety of cell types, including cells of the myelomonocytic lineage. We used the monocytic leukaemia cell line THP-1, which differentiates to macrophages in response to phorbol 12-myristate 13-acetate (PMA), to investigate the regulation by RA of genes in the scavenger receptor type B family (CD36) in human monocyte/macrophages. Reverse transcription-polymerase chain reaction and flow cytometry demonstrated that, like PMA and the natural peroxisome-proliferator-activated receptor-gamma (PPARgamma) ligand 15d-PGJ2, RA induced CD36 gene expression in these cells. Moreover, RA plus 15d-PGJ2 further enhanced CD36 protein and mRNA levels over that seen with the RA or PPARgamma compounds alone. The PPARgamma antagonist GW9662 was shown to block completely PPARgamma-ligand induction of CD36 gene expression, but had little effect on the action of RA. Our data indicated that RXR- and RAR-specific ligands (LG153 and TTNPB, respectively) were each alone able to increase CD36 mRNA and surface protein levels. By using calphostin C, a specific protein kinase C (PKC) inhibitor, we demonstrated that induction of CD36 by PMA, as well as by PPARgamma and RXR ligands were dependent upon PKC activation. In contrast, activation of CD36 through the RAR pathway was not affected by inhibition of PKC activity. Taken together, these data demonstrate that RA can up-regulate CD36 expression in human monocytes/macrophages. This regulation appears to be predominantly mediated through the RAR/RXR pathway of action and, unlike previously described methods of CD36 modulation, is independent of PPARgamma and PKC signalling. This study suggests a possible role for RA in physiological processes involving the scavenger receptor function in cells of the monocyte/macrophage lineage.
Han
Shouwei
S
Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
Sidell
Neil
N
D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D014212:Tretinoin / Q000494:pharmacology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014212:Tretinoin; D018819:Dipeptidyl Peptidase 4; D015230:Prostaglandin D2