title: Caveolin-1 plays a critical role in the differentiation of monocytes into macrophages.
abstract: OBJECTIVE
  Monocyte to macrophage differentiation is an essential step in atherogenesis. The structure protein of caveolae, caveolin-1, is increased in primary monocytes after its adhesion to endothelium. We explore the hypothesis that caveolin-1 plays a role in monocyte differentiation to macrophages.
  
  
  RESULTS
  Both phorbol myristate acetate-induced THP-1 and colony-stimulating factor-induced primary monocyte differentiation was associated with an increase in cellular caveolin-1 expression. Overexpression of caveolin-1 by transfection increased macrophage surface markers and inflammatory genes, whereas caveolin-1 knockdown by small interfering RNA or knockout reduced these. Also, caveolin-1 knockdown inhibited the differentiation-induced nuclear translocation of early growth response 1 (EGR-1) through extracellular signal-regulated kinase phosphorylation, further decreased the binding of EGR-1 to CD115 promoter, thus decreasing EGR-1 transcriptional activity. In functional assays, caveolin-1 inhibited transmigration but promoted phagocytosis in the monocyte-macrophage lineage. Decreasing caveolin-1 inhibited the uptake of modified low-density lipoprotein and reduced cellular lipid content. Finally, we showed that caveolin-1 knockout mice displayed less monocyte differentiation than wild-type mice and that EGR-1 transcription activity was also decreased in these mice because of the inhibition of extracellular signal-regulated kinase phosphorylation.
  
  
  CONCLUSIONS
  Caveolin-1 promotes monocyte to macrophage differentiation through the regulation of EGR-1 transcriptional activity, suggesting that phagocytic caveolin-1 may be critical for atherogenesis.
authors: Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia. yi.fu@bakeridi.edu.au
authors: Yi
authors: Y
authors: Fu
authors: Xiao-Lei
authors: XL
authors: Moore
authors: Man K S
authors: MK
authors: Lee
authors: Manuel A
authors: MA
authors: Fernández-Rojo
authors: Marie-Odile
authors: MO
authors: Parat
authors: Robert G
authors: RG
authors: Parton
authors: Peter J
authors: PJ
authors: Meikle
authors: Dmitri
authors: D
authors: Sviridov
authors: Jaye P F
authors: JP
authors: Chin-Dusting
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001665:Binding Sites; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D054338:Cell Transdifferentiation / Q000187:drug effects; D018920:Coculture Techniques; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate