Ethanol Extract of Oenanthe javanica Modulates Inflammatory Response by Inhibiting NF-${\kappa}B$ Mediated Cyclooxygenase-2 Expression in RAW 264.7 Macrophage

  • Lee, Jeong-Min (Department of Food & Nutrition, Nambu University) ;
  • Kim, Nam-Joo (Department of Pathology, Chonnam National University Medical School) ;
  • Cho, Dong-Hyeok (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Chung, Min-Young (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Hwang, Kwon-Tack (Department of Food & Nutrition, Nambu University) ;
  • Kim, Hyun-Ji (Department of Food & Nutrition, Nambu University) ;
  • Jun, Woo-Jin (Department of Food & Nutrition, Chonnam National University) ;
  • Park, Chang-Soo (Department of Pathology, Chonnam National University Medical School)
  • Published : 2006.04.30

Abstract

Effect of Oenanthe javanica ethanol extract (OJE) on nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-mediated inflammatory reaction in RAW 264.7 macrophage cells was investigated. The OJE dose-dependently inhibited secretions of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandins $E_2\;(PGE_2)$ from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and blocked LPS-induced expression of cyclooxygenase-2. To clarify mechanistic basis for its inhibitions of NF-${\kappa}B$ and activator protein-1 (AP-1) activations, effects of OJE on activations of NF-${\kappa}B$ and AP-1 genes by luciferase reporter activity were examined. The LPS-stimulated activations of NF-${\kappa}B$ and AP-1 were significantly blocked by 400 and $600\;{\mu$}g/mL of OJE, implicating that OJE might regulate gene expression through more than one signaling pathway. Cytosolic degradation of I-${\kappa}B{\alpha}$ was inhibited by OJE dose-dependently, indicating that the nuclear translocation of p65 was inhibited by OJE. These findings suggest that the inhibition of LPS-stimulated COX-2 expression by OJE is due to its inhibition of NF-${\kappa}B$ activation by blocking I-${\kappa}B{\alpha}$ degradation, which may be mechanistic basis of anti-inflammatory effects of OJE.

Keywords

References

  1. Smith WL, Dewitt DL, Garavito RM. Cyclooxygenase: structural, cellular, and molecular biology. Annu. Rev. Biochem. 69: 145-182 (2000) https://doi.org/10.1146/annurev.biochem.69.1.145
  2. Dixon DA, Kaplan CD, McIntyre TM, Zimmerman GA, Prescott SM. Post-transcriptional control of cyclooxygenase-2 gene expression. J. Biol. Chem. 275: 11750-11757 (2000) https://doi.org/10.1074/jbc.275.16.11750
  3. Newton R, Kuitert LM, Bergmann M, Adcock IM, Bames PJ. Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-lbeta. Biochem. Bioph. Res. Co. 237: 28-32 (1997) https://doi.org/10.1006/bbrc.1997.7064
  4. Dewitt DL, Meade EA. Serum and glucocorticoid regulation of gene transcription and expression of prostaglandin H synthase-l and prostaglandin H synthase-2 isozyms. Arch. Biochem. Biophys. 306: 94-102 (1993) https://doi.org/10.1006/abbi.1993.1485
  5. Rosen GD, Birkenmeier TM, Raz A, Holtzman MJ. Identification of a cyclooxygenase-related gene and its potential role in prostaglandin formation. Biochem. Bioph. Res. Co. 164: 1358-1365 (1989) https://doi.org/10.1016/0006-291X(89)91819-6
  6. Lim JW, Kim H, Kim KH. Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells. Lab. Invest. 81: 349-360 (2001) https://doi.org/10.1038/labinvest.3780243
  7. Billich A, Bomancin F, Mechtcheriakova D, Natt F, Huesken D, Baumruker T. Basal and induce sphingosin kinase 1 activity in A549 carcinoma cells: function in cell survival and IL-l beta and TNFalpha induced production of inflammatory mediators. Cell. Signal. 17: 1203-1317 (2005) https://doi.org/10.1016/j.cellsig.2004.12.005
  8. Gilmore TD. The $Rel/NF-{\kappa}B$ signal transduction pathway: introducion. Oncogene 18: 6842-6844 (1999) https://doi.org/10.1038/sj.onc.1203237
  9. Choi EM, Kim AJ, Hwang JK. Enhanced immune cell functions and cytokine production after in vitro stimulation with arabinoxylans fraction from rice bran. Food Sci. Biotechnol. 14: 479-486 (2005)
  10. Chouaib S, Welte K, Mertelsmann R, Dupont T. $PGE_2$ acts at two distinct pathways of T lymphocyte activation: inhibition of IL-2 production and down regulation of transferrin expression. J. Immunol, 135: 1172-1179 (1985)
  11. Kang KW, Choi SY, Cho MK, Lee CH, Kim SG. Thrombin induces nitric-oxide synthase via Galpha 12/13-coupled protein kinase Cdependent l-kappaBalpha phosphorylation and JNK-mediated 1kappaBalpha degradation. J. Biol. Chem. 278: 17368-17378 (2003) https://doi.org/10.1074/jbc.M300471200
  12. Wang WN, Yang XB, Liu HZ, Huang ZM, Wu GX. Effect of Oenanthe javanica flavone on human and duck hepatitis B virus infection. Acta Pharmacol. Sin. 26: 587-592 (2005) https://doi.org/10.1111/j.1745-7254.2005.00055.x
  13. Bai SK, Lee SJ, Na HJ, Ha KS, Han JA, Lee H, Kwon YGk, Chung CK, Kim YM. ${\beta}-carotene$ inhibits inflammatory gene expression in LPS-stimulated macrophage by suppressing redox-based $NF-{\kappa}B$ activation. Exp. Mol. Med. 37: 323-334 (2005) https://doi.org/10.1038/emm.2005.42
  14. Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of $NF-{\kappa}B$ activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid. Redox Sign. 7: 395-403 (2005) https://doi.org/10.1089/ars.2005.7.395
  15. Ching LS, Mohamed S. a-tocopherol content in 62 edible tropical plants. J. Agric. Food Chem. 49: 3101-3105 (2001) https://doi.org/10.1021/jf000891u
  16. Choi YM, Ku JB, Chang HB, Lee JS. Antioxidant activities and total phenolics of ethanol extracts from several edible mushrooms produced in Korea. Food Sci. Biotechnol. 14: 700-703 (2005)
  17. Ghosh S, May MJ, Kopp EB. $NF-{\kappa}B$ and Rei proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16:225-260 (1998) https://doi.org/10.1146/annurev.immunol.16.1.225
  18. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of $NF-{\kappa}B$ activity. Annu. Rev. Immunol. 18: 621-663 (2000) https://doi.org/10.1146/annurev.immunol.18.1.621
  19. Huang WC, Chen JJ, Chen CC. c-Src-dependent tyrosine phosphorylation of IKKbeta is involved in tumor necrosis factor-alpha-induced intercellular adhesion molecule-l expression. J. Biol. Chem. 278: 9944-9952 (2003) https://doi.org/10.1074/jbc.M208521200
  20. Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV. Protein kinase Calpha (PKCalpha) acts upstream of PKtheta to activate IKB kinase and $NF-{\kappa}B$ in T lymphocytes. Mol. Cell. BioI. 23: 7068-7081 (2003) https://doi.org/10.1128/MCB.23.19.7068-7081.2003