title: Immunoregulatory effects of AFP domains on monocyte-derived dendritic cell function.
abstract: BACKGROUND
  Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function.
  
  
  RESULTS
  As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DR high/CD11c high and CD80+/CD86 high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70).
  
  
  CONCLUSIONS
  D2- and D3- but not D1-AFP extensively suppresses the MDDC function. All the recombinant AFP proteins impaired the ability of MDDC to secrete IL-12.
authors.affiliation: Mochtar Riady Institute for Nanotechnology, Tangerang 15810, Indonesia. asetiyono@mrinstitute.org
authors.forename: Agus
authors.initials: A
authors.lastname: Setiyono
authors.forename: Akterono D
authors.initials: AD
authors.lastname: Budiyati
authors.forename: Sigit
authors.initials: S
authors.lastname: Purwantomo
authors.forename: Madonna R
authors.initials: MR
authors.lastname: Anggelia
authors.forename: Ismail
authors.initials: I
authors.lastname: Fanany
authors.forename: Gunawan A
authors.initials: GA
authors.lastname: Wibowo
authors.forename: Indra
authors.initials: I
authors.lastname: Bachtiar
authors.forename: Andi
authors.initials: A
authors.lastname: Utama
authors.forename: Susan
authors.initials: S
authors.lastname: Tai
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000276:immunology / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; C508594:IL2 protein, human; C508598:IL4 protein, human; D007376:Interleukin-2; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor