Alpha-tocopherol down-regulates scavenger receptor activity in macrophages.
The aim of this study was to investigate the effect of alpha-tocopherol on scavenger receptor (SR) activity, SR class A (SR-A) mRNA expression and transcriptional regulation in macrophages. Scavenger receptor activity was determined quantitatively by uptake of DiI-acLDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein) in rabbit peritoneal macrophages and human monocytes/macrophages in the presence and absence of different tocopherol homologues. SR-A mRNA expression was determined by Northern blotting, the activity of the transcription factor activator protein-1 (AP-1) by electrophoretic mobility shift assay. We could demonstrate that alpha-tocopherol down-regulates scavenger receptor activity in macrophages in a dose-dependent manner. Scavenger receptor activity was reduced by 13, 16, 18 and 24% in the presence of 1, 5, 10 and 50 microM alpha-tocopherol, respectively. This effect was associated with a reduced SR-A mRNA expression and activity of AP-1 binding transcription factors in the presence of alpha-tocopherol. The activity of scavenger receptors in human monocyte derived macrophages incubated with 100 microM alpha-tocopherol for 15 days was reduced up to 60%. Interestingly, gamma-tocopherol, which is a homologue of alpha-tocopherol with a comparable antioxidative capacity, showed only a weak suppression of SR activity, SR-A expression and AP-1 activity. Our observations point to the conclusion that the reduction of SR-A expression and activity in presence of alpha-tocopherol is possibly related to its direct action on cell signaling.
Teupser
D
D
Institute of Clinical Chemistry, Klinikum Grosshadern, University of Munich, Germany.
Thiery
J
J
Seidel
D
D
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects; D011817:Rabbits; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012680:Sensitivity and Specificity; D013045:Species Specificity; D014810:Vitamin E / Q000378:metabolism* / Q000494:pharmacology
C495139:MSR1 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D014810:Vitamin E