Synthetic isoforms of endogenous sulfatides differently modulate indoleamine 2,3-dioxygenase in antigen presenting cells

Emanuela Altomare, Silvia Fallarini, Carolina Orsi Battaglini, Matteo Mossotti, Luigi Panza, Grazia Lombardi

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Aims: 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. Main methods: CD1d-transfected THP-1 human cells were used as APC and treated with increasing concentrations (0.01-10 μM) 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 (RTPCR) and high performance liquid chromatography (HPLC). Compound-untreated cells were taken as negative, while 1000 U/ml interferon (IFN)-γ-treated cells as positive controls. Key findings: Not all sulfatides induced the same effect: the basal IDO1 expression was significantly reduced (-48±3% at 0.01 μ) by C16:0 sulfatide, while it was increased by C18:0 or C24:1 sulfatide (+87±7% and +50±5% at 1 μM, 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 0.01 μM), while it was increased by C18:0 or C24:1 sulfatide (+61±8% and +48±4% at 1 μM, respectively) over negative controls. C22:0 sulfatide resulted ineffective at all concentration tested. Significance: 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.

Lingua originaleInglese
pagine (da-a)176-181
Numero di pagine6
RivistaLife Sciences
Volume89
Numero di pubblicazione5-6
DOI
Stato di pubblicazionePubblicato - 1 ago 2011

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