Inhibitory Effect of Amentoflavone of Selaginella Tamariscina on MMP-9 Expression through NF-${\kappa}$B and AP-1 in Macrophage Raw 264.7 cells

  • Ahn, Byung-Tae (Cardiovascular Medical Research Center and Department of Diagnostics, Dongguk University) ;
  • Shin, Sung-Ahn (Cardiovascular Medical Research Center and Department of Diagnostics, Dongguk University) ;
  • Kim, Jun-Gi (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Park, Won-Hwan (Cardiovascular Medical Research Center and Department of Diagnostics, Dongguk University)
  • Published : 2007.02.25

Abstract

The French paradox has been attributed to the antioxidant properties of flavonoids present in the red wine. Amentoflavone(AF) is a bi-flavonoid compound with anti-fungal and anti-inflammatory activities. We isolated AF from Selaginella tamariscina, and studied its effects on nuclear factor-B(NF-B)-mediated MMP-9 gene expression in RAW264.7 cells. AF blocked the lipopolysaccharide(LPS)-induced expression of MMP-9. Zymographic and immunoblot analyses showed that AF suppressed LPS-induced MMP-9 expression in a dose-dependent manner. To clarify the mechanistic basis for its inhibition of MMP-9 induction, we examined the effect of AF on the transactivation of MMP-9 gene by luciferase reporter activity using -1.59 kb flanking region. AF potently suppressed the reporter gene activity. This inhibition was characterized by down-regulation of MMP-9, which was transcriptionally regulated at NF-B site and activation protein-1 (AP-1) site in the MMP-9 promoter, two important nuclear transcription factors that are involved in MMP-9 expression. These findings indicate the efficacy of AF in inhibiting MMP-9 expression through the transcription factors NF-B and AP-1 on LPS-induced RAW264.7 cells.

Keywords

References

  1. Z.S. Galis, M. Muszynski, G.K. Sukhova, E. Simon-Morrissey, E.N. Unemori, W.W. Lark, E. Amento and P. Libby, Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling, Circ. Res. 75:181-189, 1994 https://doi.org/10.1161/01.RES.75.1.181
  2. R.P. Fabunmi, A.H. Baker, E.J. Murray, R.F.G. Booth and A.C. Newby, Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1, -2, and -3 in rabbit aortic smooth muscle cells Biochem. J. 315:335-342, 1996 https://doi.org/10.1042/bj3150335
  3. A. Cho, J. Graves and M.A. Reidy, Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells, Arterioscler. Thromb. Vasc. Biol. 20:2527-2532, 2000 https://doi.org/10.1161/01.ATV.20.12.2527
  4. S.K. Moon, B.Y. Cha and C.H. Kim. ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway. J. Cell. Physiol. 198:417-427, 2004 https://doi.org/10.1002/jcp.10435
  5. Y. Okada, Y. Gonoji, K. Naka, K. Tomita, I. Nakanishi, K. Iwata, K. Yamashita, and T. Hayakawa, Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase from HT 1080 human fibrosarcoma cells, Purification and activation of the precursor and enzymic properties, J. Biol. Chem. 267:21712-21719, 1992
  6. R.M. Senior, G.L. Griffin, C.J. Fliszar, S.D. Shapiro, G.I. Goldberg, H.G. Welgus, Human 92- and 72-kilodalton type IV collagenases are elastases, J Biol Chem. 266:7870-7875. 1991
  7. Z.S. Galis, M. Muszynski, G.K. Sukhova, E. Simon-Morrissey, E.N. Unemori, W.W. Lark, E. Amento, and P. Libby, Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion, Circ. Res. 75:181-189, 1994 https://doi.org/10.1161/01.RES.75.1.181
  8. R.P. Fabunmi, A.H. Baker, E.J. Murray, R.F.G. Booth, and A.C. Newby, Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1, -2, and -3 in rabbit aortic smooth muscle cells, Biochem. J. 315:335-342, 1996 https://doi.org/10.1042/bj3150335
  9. H. Sato, M. Seiki, Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells, Oncogene. 8:395-405, 1993
  10. H, Sato, M. Kita, M. Seiki, v-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements. A mechanism regulating gene expression independent of that by inflammatory cytokines, J. Biol. Chem. 268:23460-23468, 1993
  11. A.R. Farina, A. Tacconelli, A. Vacca, M. Maroder, A. Gulino, A.R. Mackay, Transcriptional up-regulation of matrix metalloproteinase-9 expression during spontaneous epithelial to neuroblast phenotype conversion by SK-N-SH neuroblastoma cells, involved in enhanced invasivity, depends upon GT-box and nuclear factor kappaB elements, Cell Growth Differ. 10:353-367, 1999
  12. Gambhir, S.S., Goel, R.K., Das Gupta, G. Anti-inflammatory & anti-ulcerogenic activity of amentoflavone. Ind J Med Res. 85:689-693, 1987
  13. Kim, H.K., Son, K.H., Chang, H.W., Kang, S.S., Kim, H.P. Amentoflavone, a plant biflavone: a new potential anti-inflammatory agent. Arch Pharm Res. 21:406-410, 1998 https://doi.org/10.1007/BF02974634
  14. Tordera, M., Ferrandiz, M.L., Alcaraz, M.J. Influence of anti-inflammatory flavonoids on degranulation and arachidonic acid release in rat neutrophils. Z Naturforsch [C]. 49:235-240, 1994
  15. Huguet, A.I., Manez, S., Alcaraz, M.J. Superoxide scavenging properties of flavonoids in a non-enzymic system. Z Naturforsch [C]. 45:19-24, 1990
  16. Lee, H.S., Oh, W.K., Kim, B.Y., Ahn, S.C., Kang, D.O., Shin, D.I. et al. Inhibition of phospholipase C gamma 1 activity by amentoflavone isolated from Selaginella tamariscina. Planta Med. 62:293-296, 1996 https://doi.org/10.1055/s-2006-957887
  17. Saponara R, Bosisio E. Inhibition of cAMP-phosphodiesterase by biflavones of Ginkgo biloba in rat adipose tissue. J Nat Prod. 61:1386-1387, 1998 https://doi.org/10.1021/np970569m
  18. Banerjee, T., Valacchi, G., Ziboh, V.A., van der Vliet, A. Inhibition of TNFalpha-induced cyclooxygenase-2 expression by amentoflavone through suppression of NF-kappaB activation in A549 cells. Mol Cell Biochem. 238:105-110, 2002 https://doi.org/10.1023/A:1019963222510
  19. Woo, E.R., Lee, J.Y., Cho, I.J., Kim, S.G., Kang, K.W. Amentoflavone inhibits the induction of nitric oxide synthase by inhibiting NF-kB activation in macrophages. Pharmacological Research. 51:539-546, 2005 https://doi.org/10.1016/j.phrs.2005.02.002
  20. Kang, S.S., Kim, J.S., Kawk, W.J. and Kim, K.H. Biflavonoids from the aerial part of Lonicera japonica Kor. J. Pharmacognosy. 21:111-120, 1990
  21. Son, K.H., Park, J.O., Chung, K.C., Chang, H.W., Kim, H.P., Kim, J.S. and Kang, S.S. Flavonoids from the aerial part of Lonicera japonica. Arch. Pharm. Res. 15:365-370, 1992 https://doi.org/10.1007/BF02974114
  22. Shin, D.I. and J, Kim. Kor. J. Pharmacognosy. 22:207-210, 1991
  23. C. Patterson, J. Ruef, N.R. Madamanchi, P. Barry-Lane, Z. Hu, C. Horaist, C.A. Ballinger, A.R. Brasier, C. Bode, and M. S. Runge, Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin. Evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo, J. Biol. Chem. 274:19814-19822, 1999 https://doi.org/10.1074/jbc.274.28.19814
  24. C. Yan, H. Wang, D. Boyd, KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha -induced block of p65/p50 nuclear translocation, J. Biol. Chem. 276:1164-1172, 2001 https://doi.org/10.1074/jbc.M008681200
  25. R. Gum, E. Lengyel, J. Juarez, J.H. Chen, H. Sato, M.Seiki, D. Boyd, Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences, J. Biol. Chem. 271:10672-10680, 1996 https://doi.org/10.1074/jbc.271.18.10672
  26. P. Huhtala, A. Tuuttila, L.T. Chow, J. Lohi, J. Keski-Oja, K. Tryggvason, Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells, J. Biol. Chem. 266:16485-16490, 1991
  27. M. Bond, R.P. Fabunmi, A.H. Baker, A.C. Newby, Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B, FEBS. Lett. 435:29-34, 1998 https://doi.org/10.1016/S0014-5793(98)01034-5
  28. R Ross, Cell biology of atherosclerosis, Annu. Rev. Physiol. 57:791-804, 1995 https://doi.org/10.1146/annurev.ph.57.030195.004043
  29. A. Cho, M.A. Reidy, Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury, Circ. Res. 91:845-851, 2002 https://doi.org/10.1161/01.RES.0000040420.17366.2E
  30. Z.S. Galis, C. Johnson, D. Godin, R. Magid, J.M. Shipley, R.M. Senior, E. Ivan, Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling, Circ. Res. 91:852-859, 2002 https://doi.org/10.1161/01.RES.0000041036.86977.14