Peroxisome‐proliferator‐activated‐receptor gamma (PPARγ) independent induction of CD36 in THP‐1 monocytes by retinoic acid

Abstract

SUMMARYRetinoic 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 peroxisomeproliferator-activated receptor-c (PPARc) 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 PPARc compounds alone. The PPARc antagonist GW9662 was shown to block completely PPARc-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 PPARc 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 PPARc 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.

Up-regulation of p21 Gene Expression by Peroxisome Proliferator-Activated Receptor γ in Human Lung Carcinoma Cells

“…To amplify 474 bp PPAR␥, 354 bp p21, 323 bp cyclin D1, and 200 bp glyceraldehyde-3-phosphate dehydrogenase cDNA fragments, the sequences of PCR primers (Sigma Genosys, Woodlands, TX) were as follows: for PPAR␥ sense (5Ј-CTCTCCGTAATGGAAGACC-3Ј), antisense (5Ј-GC-ATTATGAGACATCCCCAC-3Ј); for p21 sense (5Ј-GCGAT-GGAACTTCGACTTTGT-3Ј), antisense (5Ј-GGGCTTCCTCT-TGGAGAAGAT-3Ј); for cyclin D1 sense (5Ј-GGCAACGGA-GGTCTGCG-3Ј), antisense (5Ј-GTCGGTGGTAGATGCACA-GCTT-3Ј); and for glyceraldehyde-3-phosphate dehydrogenase sense (5Ј-CCATGGAGAAGGCTGGGG-3Ј), antisense (5Ј-CA-AAGTTGTCATGGATGACC-3Ј) according to published data (31)(32)(33). RT-PCR was carried out as described previously (31). The samples were first denatured at 95°C for 30 s, followed by 32 PCR cycles, each with temperature variations as follows: 95°C for 30 s, 60°C for 30 s, and 72°C for 30 s. The last cycle was followed by an additional extension incubation of 7 min at 72°C.…”

The role of CD36 receptor in the pathogenesis of atherosclerosis

“…16 By contrast, the blockage of CD36 reduced the secretion of IL-1β, IL-6 and IL-8 and foam cell formation in human macrophages. 17 Based on the results of the above studies, it can be concluded that reduction of CD36 receptor expression on macrophages prevents the development of atherosclerosis. This has opened up the scope for further research on the regulation of CD36 expression to prevent atherosclerosis in humans.…”

All-trans retinoic acid induces oxidative phosphorylation and mitochondria biogenesis in adipocytes

“…The treatment affected as expected the expression of genes previously shown to be modulated by ATRA in adipocytes and/or adipose tissue ( Table 1 ), which validated our microarray experiments. Thus, changes brought about by ATRA treatment included the induction of Rar ␤ , Rarres1, Ucp1 and 2, Ppargc1 ␣ , Ppar ␣ , or Cyp26b1 and the repression of the leptin, resistin, Cebp ␣ , adiponectin, and Rxr ␣ genes ( 4,9,15,18,(24)(25)(26)(27).…”