Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages.
We investigated the effects of advanced glycation end products (AGEs) on the expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only the gene expression of two major OxLDL receptors, macrophage scavenger receptor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-density lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs increased transcriptional activities of AP-1, NF-kappaB, and peroxisome proliferator-activated receptor gamma. These findings indicate that AGEs-induced enhancement of these transcriptional activities might be involved in increased levels of mRNA for some of OxLDL receptors in THP-1-cells treated with PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involved in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of individuals with diabetes.
Iwashima
Y
Y
Department of Internal Medicine, Sano Hospital, Suehiro 3-3-1-15, Asahikawa, 078-8133, Japan. iwashima@msb.biglobe.ne.jp
Eto
M
M
Hata
A
A
Kaku
K
K
Horiuchi
S
S
Ushikubi
F
F
Sano
H
H
D015152:Blotting, Northern; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis / Q000235:genetics; D018110:Receptors, Lipoprotein; D051131:Receptors, Oxidized LDL; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D051127:Scavenger Receptors, Class E; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation
D018955:CD36 Antigens; D002839:Chromans; D018076:DNA, Complementary; D017127:Glycation End Products, Advanced; C495139:MSR1 protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; C495137:OLR1 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D051131:Receptors, Oxidized LDL; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D051127:Scavenger Receptors, Class E; D013844:Thiazoles; D045162:Thiazolidinediones; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077288:Troglitazone; D013755:Tetradecanoylphorbol Acetate