TY - JOUR
T1 - Synthetic isoforms of endogenous sulfatides differently modulate indoleamine 2,3-dioxygenase in antigen presenting cells
AU - Altomare, Emanuela
AU - Fallarini, Silvia
AU - Battaglini, Carolina Orsi
AU - Mossotti, Matteo
AU - Panza, Luigi
AU - Lombardi, Grazia
N1 - Funding Information:
We thank Dr. Gennaro De Libero, Department of Research, Experimental Immunology, Basel CH for providing the CD1d-transfected THP-1 cells. This study was supported by the University of “Piemonte Orientale Amedeo Avogadro” Vercelli (Italy) .
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
KW - Glycosphingolipids
KW - L-kynurenine pathway
KW - THP-1 cells
KW - Tryptophan metabolism
UR - http://www.scopus.com/inward/record.url?scp=80051789063&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2011.05.015
DO - 10.1016/j.lfs.2011.05.015
M3 - Article
SN - 0024-3205
VL - 89
SP - 176
EP - 181
JO - Life Sciences
JF - Life Sciences
IS - 5-6
ER -