The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-${\alpha}$ and IFN ${\gamma}$-stimulated Primary Cultured Astrocytes

  • Lee, Jin-Koo (Department of Pharmacology, College of Medicine, Dankook University) ;
  • Kim, Jin-Kyu (Institute of Natural Medicine, College of Medicine, Hallym University) ;
  • Park, Soo-Hyun (Institute of Natural Medicine, College of Medicine, Hallym University) ;
  • Sim, Yun-Beom (Institute of Natural Medicine, College of Medicine, Hallym University) ;
  • Jung, Jun-Sub (Institute of Natural Medicine, College of Medicine, Hallym University) ;
  • Suh, Hong-Won (Institute of Natural Medicine, College of Medicine, Hallym University)
  • Received : 2011.06.07
  • Accepted : 2011.09.24
  • Published : 2010.10.30
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Abstract

Here we have investigated how lactosylceramide (LacCer) modulates gene expression of adhesion molecules in TNF-${\alpha}$ and IFN ${\gamma}$ (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-${\kappa}B$, AP-1, GAS, and STAT-3 luciferase vectors-transfected cells. In addition, LacCer reversed the inhibition of NF-${\kappa}B$ 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-${\kappa}B$, AP-1, STAT-1, and STAT-3 in CM-stimulated astrocytes.

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References

  1. Lee SJ, Benveniste EN. Adhesion molecule expression and regulation on cells of the central nervous system. J Neuroimmunol. 1999;98:77-88. https://doi.org/10.1016/S0165-5728(99)00084-3
  2. Rosenman SJ, Shrikant P, Dubb L, Benveniste EN, Ransohoff RM. Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. J Immunol. 1995;154:1888-1899.
  3. Won JS, Singh AK, Singh I. Lactosylceramide: a lipid second messenger in neuroinflammatory disease. J Neurochem. 2007; 103 Suppl 1:180-191.
  4. Giri S, Jatana M, Rattan R, Won JS, Singh I, Singh AK. Galactosylsphingosine (psychosine)-induced expression of cytokine- mediated inducible nitric oxide synthases via AP-1 and C/EBP: implications for Krabbe disease. FASEB J. 2002;16: 661-672. https://doi.org/10.1096/fj.01-0798com
  5. Pannu R, Singh AK, Singh I. A novel role of lactosylceramide in the regulation of tumor necrosis factor alpha-mediated proliferation of rat primary astrocytes. Implications for astrogliosis following neurotrauma. J Biol Chem. 2005;280:13742-13751. https://doi.org/10.1074/jbc.M411959200
  6. Pannu R, Won JS, Khan M, Singh AK, Singh I. A novel role of lactosylceramide in the regulation of lipopolysaccharide/ interferon-gamma-mediated inducible nitric oxide synthase gene expression: implications for neuroinflammatory diseases. J Neurosci. 2004;24:5942-5954. https://doi.org/10.1523/JNEUROSCI.1271-04.2004
  7. Won JS, Im YB, Khan M, Singh AK, Singh I. The role of neutral sphingomyelinase produced ceramide in lipopolysaccharidemediated expression of inducible nitric oxide synthase. J Neurochem. 2004;88:583-593.
  8. Modur V, Zimmerman GA, Prescott SM, McIntyre TM. Endothelial cell inflammatory responses to tumor necrosis factor alpha. Ceramide-dependent and -independent mitogenactivated protein kinase cascades. J Biol Chem. 1996;271: 13094-13102. https://doi.org/10.1074/jbc.271.22.13094
  9. mediates tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 (ICAM-1) expression and the adhesion of neutrophil in human umbilical vein endothelial cells. J Biol Chem. 1998;273:34349-34357. https://doi.org/10.1074/jbc.273.51.34349
  10. Chatterjee S. Sphingolipids in atherosclerosis and vascular biology. Arterioscler Thromb Vasc Biol. 1998;18:1523-1533. https://doi.org/10.1161/01.ATV.18.10.1523
  11. Tessitore A, Pastore L, Rispoli A, Cilenti L, Toniato E, Flati V, Farina AR, Frati L, Gulino A, Martinotti S. Two gamma-interferon-activation sites (GAS) on the promoter of the human intercellular adhesion molecule (ICAM-1) gene are required for induction of transcription by IFN-gamma. Eur J Biochem. 1998;258:968-975. https://doi.org/10.1046/j.1432-1327.1998.2580968.x
  12. Lee SJ, Park JY, Hou J, Benveniste EN. Transcriptional regulation of the intercellular adhesion molecule-1 gene by proinflammatory cytokines in human astrocytes. Glia. 1999; 25:21-32. https://doi.org/10.1002/(SICI)1098-1136(19990101)25:1<21::AID-GLIA3>3.0.CO;2-R
  13. Park ES, You SH, Kim H, Kwon OY, Ro HK, Cho BY, Taniguchi SI, Kohn LD, Shong M. Hormone-dependent regulation of intercellular adhesion molecule-1 gene expression: cloning and analysis of 5'-regulatory region of rat intercellular adhesion molecule-1 gene in FRTL-5 rat thyroid cells. Thyroid. 1999;9: 601-612. https://doi.org/10.1089/thy.1999.9.601
  14. Hurwitz AA, Lyman WD, Guida MP, Calderon TM, Berman JW. Tumor necrosis factor alpha induces adhesion molecule expression on human fetal astrocytes. J Exp Med. 1992;176: 1631-1636. https://doi.org/10.1084/jem.176.6.1631
  15. Ka퀅za J, Krupi?ki J, Kumar P, Kumar S, Wang JM. VCAM-1 expression on reactive and tumour astrocytes. Folia Histochem Cytobiol. 1994;32:17-20.
  16. Hery C, Sebire G, Peudenier S, Tardieu M. Adhesion to human neurons and astrocytes of monocytes: the role of interaction of CR3 and ICAM-1 and modulation by cytokines. J Neuroimmunol. 1995;57:101-109. https://doi.org/10.1016/0165-5728(94)00168-N
  17. Vitolo D, Paradiso P, Uccini S, Ruco LP, Baroni CD. Expression of adhesion molecules and extracellular matrix proteins in glioblastomas: relation to angiogenesis and spread. Histopathology. 1996;28:521-528. https://doi.org/10.1046/j.1365-2559.1996.d01-471.x
  18. Lee JH, Kim CH, Seo GH, Lee J, Kim JH, Kim DG, Ahn YS. Heparin attenuates the expression of TNF alpha-induced cerebral endothelial cell adhesion molecule. Korean J Physiol Pharmacol. 2008;12:231-236. https://doi.org/10.4196/kjpp.2008.12.5.231
  19. Ginis I, Schweizer U, Brenner M, Liu J, Azzam N, Spatz M, Hallenbeck JM. TNF-alpha pretreatment prevents subsequent activation of cultured brain cells with TNF-alpha and hypoxia via ceramide. Am J Physiol. 1999;276:C1171-1183. https://doi.org/10.1152/ajpcell.1999.276.5.C1171
  20. Chang YJ, Holtzman MJ, Chen CC. Interferon-gamma-induced epithelial ICAM-1 expression and monocyte adhesion. Involvement of protein kinase C-dependent c-Src tyrosine kinase activation pathway. J Biol Chem. 2002;277:7118-7426. https://doi.org/10.1074/jbc.M109924200
  21. Park EJ, Ji KA, Jeon SB, Choi WH, Han IO, You HJ, Kim JH, Jou I, Joe EH. Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-gamma-stimulated rat astrocytes. J Immunol. 2004;173:5697-5703. https://doi.org/10.4049/jimmunol.173.9.5697
  22. Qin H, Niyongere SA, Lee SJ, Baker BJ, Benveniste EN. Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes. J Immunol. 2008;181:3167-3176. https://doi.org/10.4049/jimmunol.181.5.3167
  23. Ahmad M, Theofanidis P, Medford RM. Role of activating protein-1 in the regulation of the vascular cell adhesion molecule-1 gene expression by tumor necrosis factor-alpha. J Biol Chem. 1998;273:4616-4621. https://doi.org/10.1074/jbc.273.8.4616
  24. Lee SJ, Hou J, Benveniste EN. Transcriptional regulation of intercellular adhesion molecule-1 in astrocytes involves NFkappaB and C/EBP isoforms. J Neuroimmunol. 1998;92: 196-207. https://doi.org/10.1016/S0165-5728(98)00209-4
  25. Chen C, Chou C, Sun Y, Huang W. Tumor necrosis factor alpha-induced activation of downstream NF-kappaB site of the promoter mediates epithelial ICAM-1 expression and monocyte adhesion. Involvement of PKCalpha, tyrosine kinase, and IKK2, but not MAPKs, pathway. Cell Signal. 2001;13:543-553. https://doi.org/10.1016/S0898-6568(01)00171-1
  26. Lee YW, Kuhn H, Hennig B, Neish AS, Toborek M. IL- 4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells. J Mol Cell Cardiol. 2001;33: 83-94 https://doi.org/10.1006/jmcc.2000.1278
  27. Lazzerini G, Del Turco S, Basta G, O'Loghlen A, Zampolli A, Caterina RD. Prominent role of NF-kappaB in the induction of endothelial activation by endogenous nitric oxide inhibition. Nitric Oxide. 2009;21:184-191. https://doi.org/10.1016/j.niox.2009.07.007
  28. Yeh LH, Kinsey AM, Chatterjee S, Alevriadou BR. Lactosylceramide mediates shear-induced endothelial superoxide production and intercellular adhesion molecule-1 expression. J Vasc Res. 2001;38:551-559. https://doi.org/10.1159/000051091
  29. Pastores GM, Giraldo P, Cherin P, Mehta A. Goal-oriented therapy with miglustat in Gaucher disease. Curr Med Res Opin. 2009;25:23-37 https://doi.org/10.1185/03007990802576518
  30. Huang WC, Tsai CC, Chen CL, Chen TY, Chen YP, Lin YS, Lu PJ, Lin CM, Wang SH, Tsao CW, Wang CY, Cheng YL, Hsieh CY, Tseng PC, Lin CF. Glucosylceramide synthase inhibitor PDMP sensitizes chronic myeloid leukemia T315I mutant to Bcr-Abl inhibitor and cooperatively induces glycogen synthase kinase-3-regulated apoptosis. FASEB J. 2011;25: 3661-3673. https://doi.org/10.1096/fj.10-180190
  31. Baran Y, Bielawski J, Gunduz U, Ogretmen B. Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation. J Cancer Res Clin Oncol. 2011;137:1535-1544. https://doi.org/10.1007/s00432-011-1016-y

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