Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-alpha and IFNgamma-stimulated Primary Cultured Astrocytes.
10.4196/kjpp.2011.15.5.251
- Author:
Jin Koo LEE
1
;
Jin Kyu KIM
;
Soo Hyun PARK
;
Yun Beom SIM
;
Jun Sub JUNG
;
Hong Won SUH
Author Information
1. Department of Pharmacology, College of Medicine, Dankook University, Cheonan 330-714, Korea.
- Publication Type:Original Article
- Keywords:
ICAM-1;
VCAM-1;
D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol;
Lactosylceramide;
Astrocytes
- MeSH:
1-Deoxynojirimycin;
Antigens, CD;
Astrocytes;
Galactosyltransferases;
Gene Expression;
Glucosyltransferases;
Intercellular Adhesion Molecule-1;
Lactosylceramides;
Luciferases;
Morpholines;
NF-kappa B;
Oligonucleotides, Antisense;
Transcription Factor AP-1;
Transcription Factors;
Tumor Necrosis Factor-alpha;
Vascular Cell Adhesion Molecule-1
- From:The Korean Journal of Physiology and Pharmacology
2011;15(5):251-258
- CountryRepublic of Korea
- Language:English
-
Abstract:
Here we have investigated how lactosylceramide (LacCer) modulates gene expression of adhesion molecules in TNF-alpha and IFNgamma (CM)-stimulated astrocytes. We have observed that stimulation of astrocytes with CM increased the gene expression of ICAM-1 and VCAM-1. D-Threo-1-phenyl- 2-decanoylamino-3-morpholino-1-propanol (PDMP) and N-butyldeoxynojirimycin (NBDNJ), inhibitors of glucosylceramide synthase (GLS) and LacCer synthase (galactosyltransferase, GalT-2), inhibited the gene expression of ICAM-1 and VCAM-1 and activation of their gene promoter induced by CM, which were reversed by exogenously supplied LacCer. Silencing of GalT-2 gene using its antisense oligonucleotides also attenuated CM-induced ICAM-1 and VCAM-1 expression, which were reversed by LacCer. PDMP treatment and silencing of GalT-2 gene significantly reduced CM-induced luciferase activities in NF-KB, AP-1, GAS, and STAT-3 luciferase vectors-transfected cells. In addition, LacCer reversed the inhibition of NF-KB and STAT-1 luciferase activities by PDMP. Taken together, our results suggest that LacCer may play a crucial role in the expression of ICAM-1 and VCAM-1 via modulating transcription factors, such as NF-KB, AP-1, STAT-1, and STAT-3 in CM-stimulated astrocytes.
