| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 147, 278-292, Copyright © 1995 by American Society for Investigative Pathology
REGULAR ARTICLES |
ME Gerritsen, WW Carley, GE Ranges, CP Shen, SA Phan, GF Ligon and CA Perry
Institute for Bone and Joint Disease and Cancer, Bayer Corporation, West Haven, Connecticut 06516, USA.
Treatment of human endothelial cells with cytokines such as interleukin- 1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present study we report that cotreatment of human endothelial cells with certain hydroxyflavones and flavanols blocks cytokine- induced ICAM-1, VCAM-1, and E-selectin expression on human endothelial cells. One of the most potent flavones, apigenin, exhibited a dose- and time-dependent, reversible effect on adhesion protein expression as well as inhibiting adhesion protein upregulation at the transcriptional level. Apigenin also inhibited IL-1 alpha-induced prostaglandin synthesis and TNF-alpha-induced IL-6 and IL-8 production, suggesting that the hydroxyflavones may act as general inhibitors of cytokine- induced gene expression. Although apigenin did not inhibit TNF-alpha- induced nuclear translocation of NF-kappa B(p50(NFKB1)/p65(RelA)) we found this flavonoid did inhibit TNF-alpha induced beta-galactosidase activity in SW480 cells stably transfected with a beta-galactosidase reporter construct driven by four NF-kappa B elements, suggesting an action on NF-kappa B transcriptional activation. Adhesion of leukocytes to cytokine-treated endothelial cells was blocked in endothelial cells cotreated with apigenin. Finally, apigenin demonstrated potent anti- inflammatory activity in carrageenan induced rat paw edema and delayed type hypersensitivity in the mouse. We conclude that flavonoids offer important therapeutic potential for the treatment of a variety of inflammatory diseases involving an increase in leukocyte adhesion and trafficking.
This article has been cited by other articles:
 |
|
 |
|
  C. Nicholas, S. Batra, M. A. Vargo, O. H. Voss, M. A. Gavrilin, M. D. Wewers, D. C. Guttridge, E. Grotewold, and A. I. Doseff Apigenin Blocks Lipopolysaccharide-Induced Lethality In Vivo and Proinflammatory Cytokines Expression by Inactivating NF-{kappa}B through the Suppression of p65 Phosphorylation J. Immunol., November 15, 2007; 179(10): 7121 - 7127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Luyendyk, J. D. Piper, M. Tencati, K. V. Reddy, T. Holscher, R. Zhang, J. Luchoomun, X. Chen, W. Min, C. Kunsch, et al. A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1857 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Lotito and B. Frei Dietary Flavonoids Attenuate Tumor Necrosis Factor {alpha}-induced Adhesion Molecule Expression in Human Aortic Endothelial Cells: STRUCTURE-FUNCTION RELATIONSHIPS AND ACTIVITY AFTER FIRST PASS METABOLISM J. Biol. Chem., December 1, 2006; 281(48): 37102 - 37110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Sawatzky, D. A. Willoughby, P. R. Colville-Nash, and A. G. Rossi The Involvement of the Apoptosis-Modulating Proteins ERK 1/2, Bcl-xL and Bax in the Resolution of Acute Inflammation in Vivo Am. J. Pathol., January 1, 2006; 168(1): 33 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kunsch, J. Luchoomun, X.-l. Chen, G. L. Dodd, K. S. Karu, C. Q. Meng, E. M. Marino, L. K. Olliff, J. D. Piper, F.-H. Qiu, et al. J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 492 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Chen, M.-P. Chow, W.-C. Huang, Y.-C. Lin, and Y.-J. Chang Flavonoids Inhibit Tumor Necrosis Factor-{alpha}-Induced Up-Regulation of Intercellular Adhesion Molecule-1 (ICAM-1) in Respiratory Epithelial Cells through Activator Protein-1 and Nuclear Factor-{kappa}B: Structure-Activity Relationships Mol. Pharmacol., September 1, 2004; 66(3): 683 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Choi, Y.-J. Choi, S.-H. Park, J.-S. Kang, and Y.-H. Kang Flavones Mitigate Tumor Necrosis Factor-{alpha}-Induced Adhesion Molecule Upregulation in Cultured Human Endothelial Cells: Role of Nuclear Factor-{kappa}B J. Nutr., May 1, 2004; 134(5): 1013 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kunsch, J. Luchoomun, J. Y. Grey, L. K. Olliff, L. B. Saint, R. F. Arrendale, M. A. Wasserman, U. Saxena, and R. M. Medford Selective Inhibition of Endothelial and Monocyte Redox-Sensitive Genes by AGI-1067: A Novel Antioxidant and Anti-Inflammatory Agent J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 820 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Balestrieri, D. Castaldo, C. Balestrieri, L. Quagliuolo, A. Giovane, and L. Servillo Modulation by flavonoids of PAF and related phospholipids in endothelial cells during oxidative stress J. Lipid Res., February 1, 2003; 44(2): 380 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. KOTANIDOU, A. XAGORARI, E. BAGLI, P. KITSANTA, T. FOTSIS, A. PAPAPETROPOULOS, and C. ROUSSOS Luteolin Reduces Lipopolysaccharide-induced Lethal Toxicity and Expression of Proinflammatory Molecules in Mice Am. J. Respir. Crit. Care Med., March 15, 2002; 165(6): 818 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Koga and M. Meydani Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells Am. J. Clinical Nutrition, May 1, 2001; 73(5): 941 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Xagorari, A. Papapetropoulos, A. Mauromatis, M. Economou, T. Fotsis, and C. Roussos Luteolin Inhibits an Endotoxin-Stimulated Phosphorylation Cascade and Proinflammatory Cytokine Production in Macrophages J. Pharmacol. Exp. Ther., January 1, 2001; 296(1): 181 - 187. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Middleton Jr., C. Kandaswami, and T. C. Theoharides The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer Pharmacol. Rev., December 1, 2000; 52(4): 673 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Harnish, M. S. Scicchitano, S. J. Adelman, C. R. Lyttle, and S. K. Karathanasis The Role of CBP in Estrogen Receptor Cross-Talk with Nuclear Factor-{kappa}B in HepG2 Cells Endocrinology, September 1, 2000; 141(9): 3403 - 3411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kobuchi, S. Roy, C. K. Sen, H. G. Nguyen, and L. Packer Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway Am J Physiol Cell Physiol, September 1, 1999; 277(3): C403 - C411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Murase, N. Kume, T. Hase, Y. Shibuya, Y. Nishizawa, I. Tokimitsu, and T. Kita Gallates Inhibit Cytokine-Induced Nuclear Translocation of NF-{kappa}B and Expression of Leukocyte Adhesion Molecules in Vascular Endothelial Cells Arterioscler. Thromb. Vasc. Biol., June 1, 1999; 19(6): 1412 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O'Hara, D. Kiefer, K. Farrell, and K. Kemper A Review of 12 Commonly Used Medicinal Herbs Arch Fam Med, November 1, 1998; 7(6): 523 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Pierce, R. Schoenleber, G. Jesmok, J. Best, S. A. Moore, T. Collins, and M. E. Gerritsen Novel Inhibitors of Cytokine-induced Ikappa Balpha Phosphorylation and Endothelial Cell Adhesion Molecule Expression Show Anti-inflammatory Effects in Vivo J. Biol. Chem., August 22, 1997; 272(34): 21096 - 21103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wolle, R. R. Hill, E. Ferguson, L. J. Devall, B.K. Trivedi, R. S. Newton, and U. Saxena Selective Inhibition of Tumor Necrosis Factor–Induced Vascular Cell Adhesion Molecule-1 Gene Expression by a Novel Flavonoid: Lack of Effect on Transcription Factor NF-{kappa}B Arterioscler. Thromb. Vasc. Biol., December 1, 1996; 16(12): 1501 - 1508. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
