Interleukin-18 and interleukin-12 together downregulate ATP-binding cassette transporter A1 expression through the interleukin-18R/nuclear factor-κB signaling pathway in THP-1 macrophage-derived foam cells.
Circ J
; 76(7): 1780-91, 2012.
Article
en En
| MEDLINE
| ID: mdl-22498566
ABSTRACT
BACKGROUND:
Interleukin (IL)-18 and IL-12 synergize for the production of interferon (IFN)-γ, which can downregulate ATP-binding cassette transporter A1 (ABCA1) expression. The aim of the present study was to investigate the effect of IL-18 and/or IL-12 on ABCA1 expression. METHODS ANDRESULTS:
IL-18 combined with IL-12 decreased ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells, whereas IL-18 or IL-12 alone had no effect. IL-12 increased IL-18 receptor (IL-18R) expression, which was suppressed by small interfering RNA (siRNA) for signal transducer and activator of transcription 3. IL-18R but not IL-12 receptor siRNA completely reversed the effects of IL-18 and IL-12 on ABCA1 expression and cellular cholesterol efflux. Treatment with IL-18 plus IL-12 markedly augmented nuclear translocation of nuclear factor (NF)-κB but had no effect on expression and activity of liver X receptor α. IL-18 and IL-12 also significantly increased zinc finger protein 202 (ZNF202) levels and IFN-γ secretion. Furthermore, siRNA for ZNF202 or IFN-γ significantly impaired IL-18/IL-12-induced suppression of ABCA1, whereas NF-κB siRNA treatment blocked IL-18/IL-12' action on ZNF202 levels, IFN-γ secretion, and ABCA1 expression.CONCLUSIONS:
IL-18 and IL-12 together can decrease ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells through the IL-18R/NF-κB signaling pathway.
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Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
FN-kappa B
/
Interleucina-12
/
Transportadoras de Casetes de Unión a ATP
/
Interleucina-18
/
Receptores de Interleucina-18
/
Células Espumosas
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Circ J
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China