YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Modulatory Effect of BAY11-7082 on CD29-mediated Cell-cell Adhesion in Monocytic U937 Cells

BAY11-7082에 의한 U937 세포의 CD29-매개성 세포간 유착과정 조절 효과

  • Kim, Byung-Hun (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University)
  • 김병훈 (강원대학교 BT학부대학 생명공학부) ;
  • 조재열 (강원대학교 BT학부대학 생명공학부)
  • Published : 2008.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

Keywords

References

  1. Tetley, T. D. : Inflammatory cells and chronic obstructive pulmonary disease. Curr. Drug. Targets Inflamm Allergy 4, 607 (2005) https://doi.org/10.2174/156801005774912824
  2. Edwards, J. P., Zhang, X., Frauwirth, K. A. and Mosser, D. M. : Biochemical and functional characterization of three activated macrophage populations. J. Leukoc. Biol. 80, 1298 (2006) https://doi.org/10.1189/jlb.0406249
  3. Murtaugh, M. P. and Foss, D. L. : Inflammatory cytokines and antigen presenting cell activation. Vet. Immunol. Immunopathol. 87, 109 (2002) https://doi.org/10.1016/S0165-2427(02)00042-9
  4. Caulfield, J. J., Fernandez, M. H., Sousa, A. R., Lane, S. J., Lee, T. H. and Hawrylowicz, C. M. : Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids. Immunology 98, 104 (1999) https://doi.org/10.1046/j.1365-2567.1999.00862.x
  5. Pierce, J. W., Schoenleber, R., Jesmok, G., Best, J., Moore, S. A., Collins, T. and Gerritsen, M. E. : Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J. Biol. Chem. 272, 21096 (1997) https://doi.org/10.1074/jbc.272.34.21096
  6. Cordes, N. and Park, C. C. : beta1 integrin as a molecular therapeutic target. Int. J. Radiat. Biol. 83, 753 (2007) https://doi.org/10.1080/09553000701639694
  7. Cho, J. Y., Kim, A. R., Joo, H. G., Kim, B. H., Rhee, M. H., Yoo, E. S., Katz, D. R., Chain, B. M. and Jung, J. H. : Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions. Biochem. Biophys. Res. Commun. 313, 954 (2004) https://doi.org/10.1016/j.bbrc.2003.12.026
  8. Cho, J. Y. : Chloroquine, an anti-malarial agent, acts as a novel regulator of beta 1-integrin-mediated cell-cell adhesion. Biol. Pharm. Bull. 31, 726 (2008) https://doi.org/10.1248/bpb.31.726
  9. Cho, J. Y., Baik, K. U., Jung, J. H. and Park, M. H. : In vitro antiinflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur. J. Pharmacol. 398, 399 (2000) https://doi.org/10.1016/S0014-2999(00)00337-X
  10. Cho, J. Y., Fox, D. A., Horejsi, V., Sagawa, K., Skubitz, K. M., Katz, D. R. and Chain, B. : The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood 98, 374 (2001) https://doi.org/10.1182/blood.V98.2.374
  11. Lee, Y. G., Byeon, S. E., Kim, J. Y., Lee, J. Y., Rhee, M. H., Hong, S., Wu, J. C., Lee, H. S., Kim, M. J., Cho, D. H. and Cho, J. Y. : Immunomodulatory effect of Hibiscus cannabinus extract on macrophage functions. J. Ethnopharmacol. 113, 62 (2007) https://doi.org/10.1016/j.jep.2007.04.019
  12. Lee, Y. G., Lee, W. M., Kim, J. Y., Lee, J. Y., Lee, I. K., Yun, B. S., Rhee, M. H. and Cho, J. Y. : Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br. J. Pharmacol. 154, 852 (2008) https://doi.org/10.1038/bjp.2008.136
  13. Kim, A. R., Cho, J. Y., Zou, Y., Choi, J. S. and Chung, H. Y. : Flavonoids differentially modulate nitric oxide production pathways in lipopolysaccharide-activated RAW264.7 cells. Arch. Pharm. Res. 28, 297 (2005) https://doi.org/10.1007/BF02977796
  14. Stonehouse, T. J., Woodhead, V. E., Herridge, P. S., Ashrafian, H., George, M., Chain, B. M. and Katz, D. R. : Molecular characterization of U937-dependent T-cell co-stimulation. Immunology 96, 35 (1999) https://doi.org/10.1046/j.1365-2567.1999.00670.x
  15. Woodhead, V. E., Stonehouse, T. J., Binks, M. H., Speidel, K., Fox, D. A., Gaya, A., Hardie, D., Henniker, A. J., Horejsi, V., Sagawa, K., Skubitz, K. M., Taskov, H., Todd, R. F., 3rd van Agthoven, A., Katz, D. R. and Chain, B. M. : Novel molecular mechanisms of dendritic cell-induced T cell activation. Int. Immunol. 12, 1051 (2000) https://doi.org/10.1093/intimm/12.7.1051
  16. Longhurst, C. M. and Jennings, L. K. : Integrin-mediated signal transduction. Cell. Mol. Life Sci. 54, 514 (1998) https://doi.org/10.1007/s000180050180