title: Synthetic isoforms of endogenous sulfatides differently modulate indoleamine 2,3-dioxygenase in antigen presenting cells.
abstract: OBJECTIVE
  To investigate whether sulfatides modulate indoleamine 2,3-dioxygenase (IDO)1, a fine-tuned enzymatic mechanism for controlling immune responses, gene expression/function in antigen presenting cells (APC). The relationship between structure and activity (SAR) of newly synthesized sulfatide isoforms (C16:0, C18:0, C22:0, C24:1) was also evaluated.
  
  
  METHODS
  CD1d-transfected THP-1 human cells were used as APC and treated with increasing concentrations (0.01-10μΜ) of each compound for an appropriate period of time. The gene expression and the enzymatic activity of IDO1 were examined using reverse transcription-polymerase chain reaction (RT-PCR) and high performance liquid chromatography (HPLC). Compound-untreated cells were taken as negative, while 1000U/ml interferon (IFN)-γ-treated cells as positive controls.
  
  
  RESULTS
  Not all sulfatides induced the same effect: the basal IDO1 expression was significantly reduced (-48 ± 3% at 0.01μΜ) by C16:0 sulfatide, while it was increased by C18:0 or C24:1 sulfatide (+87 ± 7% and +50 ± 5% at 1μΜ, respectively) over negative controls; C22:0 sulfatide resulted ineffective at all concentrations tested. These effects functionally correlated with changes in IDO1 activity: l-kynurenine contents in the culture media were significantly reduced by C16:0 sulfatide (-29 ± 4% at 0.01μM), while it was increased by C18:0 or C24:1 sulfatide (+61 ± 8% and +48 ± 4% at 1μM, respectively) over negative controls. C22:0 sulfatide resulted ineffective at all concentration tested.
  
  
  CONCLUSIONS
  The overall data demonstrate that specific sulfatide isoforms differently modulate IDO1 in APC. The sulfatide-induced effects are structurally dependent on the length/saturation of their fatty acid chain.
authors.affiliation: DISCAFF, University of “Piemonte Orientale Amedeo Avogadro”, Via Giovanni Bovio, Novara, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Altomare
authors.forename: Silvia
authors.initials: S
authors.lastname: Fallarini
authors.forename: Carolina Orsi
authors.initials: CO
authors.lastname: Battaglini
authors.forename: Matteo
authors.initials: M
authors.lastname: Mossotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Panza
authors.forename: Grazia
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000201:enzymology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000378:metabolism*; D007536:Isomerism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D013433:Sulfoglycosphingolipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016328:NF-kappa B; D012333:RNA, Messenger; D013433:Sulfoglycosphingolipids; D014364:Tryptophan; D004247:DNA