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Inhibitory Effects of Propenone Derivatives on $NF-{\kappa}B$ activity and IL-8-Induced Monocyte Adhesion to Colon Epithelial Cells  

Park, Su-Young (College of Pharmacy, Yeungnam University)
Kim, Kyoung-Jin (College of Pharmacy, Yeungnam University)
Lee, Jong-Suk (College of Pharmacy, Yeungnam University)
Lee, Eung-Seok (College of Pharmacy, Yeungnam University)
Kim, Jung-Ae (College of Pharmacy, Yeungnam University)
Publication Information
YAKHAK HOEJI / v.52, no.1, 2008 , pp. 62-66 More about this Journal
Abstract
In this study, we examined the inhibitory effects of propenone derivatives, 1,3-diphenyl-propenone (DPhP), 3-phenyl-1-thiophen-2-yl-propenone (PhT2P), 3-phenyl-1-thiophen-3-yl-propenone (PhT3P) and 1-furan-2-yl-3-phenyl-propenone (FPhP), on $TNF-{\alpha}$-induced nuclear factor (NF)-${\kappa}B$ activity and interleukin (IL)-8-induced monocyte adhesion to colon epithelial cells. 1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) that is previously reported as a $NF-{\kappa}B$ inhibitor suppressed $TNF-{\alpha}$-induced monocyte-epithelial cell adhesion in a concentration-dependent manner. The propenone derivatives, DPhP, PhT2P, PhT3P, FPhP, also inhibited $TNF-{\alpha}$-induced $NF-{\kappa}B$ activation in a similar degree to FPP-3. In a DPPH radical scavenging assay, none of the compounds showed DPPH radical scavenging activity, indicating that the inhibitory actions of the propenone derivatives on redox-sensitive $NF-{\kappa}B$ activity is not due to a simple free radical scavenging activity. In addition, the propenone derivatives also suppressed the IL-8-induced monocyte adhesion to colon epithelial cells. Furthermore, the effective concentrations of the propenone derivatives on both $NF-{\kappa}B$ activation as well as IL-8 induced monocyte-epithelial cell adhesion were 1000 times lower than 5-aminosalicylic acid (5-ASA), a clinically used drug for inflammatory bowel disease. These results suggest that the propenone derivatives may be a potential lead having a strong inhibitory activity against inflammatory cytokine-induced epithelial inflammation.
Keywords
$TNF-{\alpha}$$NF-{\kappa}B$; propenone; interleukin-8; 5-aminosalicylic acid;
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1 Schreiber, S., Campieri, M., Colombel, J. F., Van Deventer, S. J., Feagan, B., Fedorak, R., Forbes, A., Gassull, M., Gendre, J. P., Van Hogezand, R. A., Lofberg, R., Modigliani, R., Pallone, F., Petritsch, W., Prantera, C., Rampton, D., Seibold, F., Vatn, M., Zeitz, M. and Rutgeerts, P. : Use of anti-tumour necrosis factor agents in inflammatory bowel disease. Int. J. Colorectal. Dis. 16, 1 (2001)
2 Kim, Y. S., Kim, J. S., Jung, H. C. and Song, I. S. : The effects of thalidomide on the stimulation of NF-kappaB activity and TNF-alpha production by lipopolysaccharide in a human colonic epithelial cell line. Mol. Cells 17, 210 (2004)
3 Reinecker, H. C., Loh, E. Y., Ringler, D. J., Mehta, A., Rombeau, J. L. and MacDermott, R. P. : Monocytechemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology 108, 40 (1995)
4 Daig, R., Andus, T., Aschenbrenner, E., Falk, W., Scholmerich, J. and Gross, V. : Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut. 38, 216 (1996)
5 Van Grevenstein, W. M. U., Hofland, L. J., Van Rossen, M. E. E., Van Koetsveld, P. M., Jeekel, J. and Van Eijck, C. H. J. : Inflammatory cytokines stimulate the adhesion of colon carcinoma cells to mesothelial monolayers. Dig. Dis. Sci. 52, 2775 (2007)
6 MacDermott, R. P. : Alterations of the mucosal immune system in inflammatory bowel disease. J. Gastroenterol. 31, 907 (1996)
7 Panja, A., Goldberg, S., Eckmann, L., Krishen, P. and Mayer, L. : The regulation and functional consequence of proinflammatory cytokine binding on human intestinal epithelial cells. J. Immunol. 161, 3675 (1998)
8 Lee, E. S., Ju, H. K., Moon, T. C., Lee, E., Jahng, Y., Lee, S. H., Son, J. K., Baek, S. H. and Chang, H. W. : Inhibition of nitric oxide and tumor necrosis factor-alpha (TNF-alpha) production by propenone compound through blockade of nuclear factor (NF)-kappa B activation in cultured murine macrophages. Biol. Pharm. Bull. 27, 617 (2004)
9 Zareie, M., Singh, P. K., Irvine, E. J., Sherman, P. M., McKay, D. M. and Perdue, M. H. : Monocyte/macrophage activation by normal bacteria and bacterial products: implications for altered epithelial function in Crohn's disease. Am. J. Pathol. 158, 1101 (2001)   DOI   ScienceOn
10 Jobin, C., Bradham, C. A., Russo, M. P., Juma, B., Narula, A. S., Brenner, D. A. and Sartor, R. B. : Curcumin blocks cytokinemediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J. Immunol. 163, 3474 (1999)
11 Aljada, A., Ghanim, H., Saadeh, R. and Dandona, P. : Insulin inhibits NFkappaB and MCP-1 expression in human aortic endothelial cells. J. Clin. Endocrinol. Meta. 86, 450 (2001)
12 Hohensinner, P. J., Kaun, C., Rychli, K., Niessner, A., Pfaffenberger, S., Rega, G., Martin, R., Maurer, G., Ullrich, R., Huber, K. and Wojta, J. : Macrophage colony stimulating factor expression in human cardiac cells is upregulated by tumor necrosis factor-alpha via an NF-kappaB dependent mechanism. J. Thromb. Haemost. 5, 2520 (2007)
13 Izzo, R. S., Witkon, K., Chen, A. I., Hadjiyane, C., Weinstein, M. I. and Pellecchia, C. : Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis. Am. J. Gastroenterol. 87, 1447 (1992)
14 Kang, D. G., Moon, M. K., Lee, A. S., Kwon, T. O., Kim, J. S. and Lee, H. S. : Cornuside suppresses cytokine-induced proinflammatory and adhesion molecules in the human umbilical vein endothelial cells. Biol. Pharm. Bull. 30, 1796 (2007)
15 Mazzucchelli, L., Hauser, C., Zgraggen, K., Wagner, H., Hess, M., Laissue, J. A. and Mueller, C. : Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am. J. Pathol. 144, 997 (1994)
16 Neurath, M. F., Fuss, I., Schurmann, G., Pettersson, S., Arnold, K., Muller-Lobeck, H., Strober, W., Herfarth, C. and Buschenfelde, K. H. : Cytokine gene transcription by NFkappa B family members in patients with inflammatory bowel disease. Ann. NY Acad. Sci. 17, 149 (1998)
17 Begue, B., Wajant, H., Bambou, J, C., Dubuquoy, L., Siegmund, D., Beaulieu, J. F., Canioni, D., Berrebi, D., Brousse, N., Desreumaux, P., Schmitz, J., Lentze, M. J., Goulet, O., Nadine, C. B. and Ruemmele, F. M. : Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions. Gastroenterology 130, 1962 (2006)
18 Grimm, M. C., Elsbury, S. K., Pavli, P. and Doe, W. F. : Interleukin 8: cells of origin in inflammatory bowel disease. Gut. 38, 90 (1996)
19 Lee, E. S., Park, B. C., Paek, S. H., Lee, Y. S., Basnet, A., Jin, D. Q., Choi, H. G., Yong, C. S. and Kim, J. A. : Potent analgesic and anti-inflammatory activities of 1-furan-2-yl-3-pyridin-2-ylpropenone with gastric ulcer sparing effect. Biol. Pharm. Bull. 29, 361 (2006)