Fisheries and Aquatic Sciences

한국수산과학회 (The Korean Society of Fisheries and Aquatic Science)
권호 표지
DOI QR코드

DOI QR Code

Ethanolic Extract of Chondria crassicaulis Inhibits the Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in LPS-Stimulated RAW 264.7 Macrophages

  • Kim, Yeon-Kye (Food and Safety Research Division, National Fisheries Research and Development Institute) ;
  • Jeong, Eun-Ji (Department of Food Science and Nutrition, Pukyong National University) ;
  • Lee, Min-Sup (Department of Food Science and Nutrition, Pukyong National University) ;
  • Yoon, Na-Young (Food and Safety Research Division, National Fisheries Research and Development Institute) ;
  • Yoon, Ho-Dong (Food and Safety Research Division, National Fisheries Research and Development Institute) ;
  • Kim, Jae-Il (Department of Food Science and Nutrition, Pukyong National University) ;
  • Kim, Hyeung-Rak (Department of Food Science and Nutrition, Pukyong National University)
  • 투고 : 2011.09.15
  • 심사 : 2011.11.10
  • 발행 : 2011.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been implicated in various inflammatory diseases. In this study, we investigated the anti-inflammatory activities of Chondria crassicaulis ethanolic extract (CCE) by measuring its effects on the expression of iNOS and COX-2 proteins in lipopolysaccharide (LPS)-treated RAW 264.7 murine macrophages. CCE significantly and dose-dependently inhibited the LPS-induced release of nitric oxide and prostaglandin $E_2$, and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells, without causing any cytotoxicity. It also inhibited the production of the pro-inflammatory cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ in LPS-stimulated RAW 264.7 cells. Moreover, treatment with CCE strongly suppressed nuclear factor-${\kappa}B$ (NF-${\kappa}B$) promoter-driven expression in LPS-treated RAW 264.7 cells. CCE treatment blocked nuclear translocation of the p65 subunit of NF-${\kappa}B$ by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that CCE regulates iNOS and COX-2 expression through NF-${\kappa}B$-dependent transcriptional control, and identifies potential candidates for the treatment or prevention of inflammatory diseases.

키워드

참고문헌

  1. Abad MJ, Bedoya LM and Bermejo P. 2008. Natural marine anti-inflammatory products. Mini Rev Med Chem 8, 740-754. https://doi.org/10.2174/138955708784912148
  2. Beutler B and Cerami A. 1989. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol 7, 625-655. https://doi.org/10.1146/annurev.iy.07.040189.003205
  3. Blunt JW, Copp BR, Munro MH, Northcote PT and Prinsep MR. 2010. Marine natural products. Nat Prod Rep 27, 165-237. https://doi.org/10.1039/b906091j
  4. Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D and Maniatis T. 1995. Signal-induced site-specific phosphorylation targets $I{\kappa}B{\alpha}$ to the ubiquitin-proteasome pathway. Genes Dev 9, 1586-1597. https://doi.org/10.1101/gad.9.13.1586
  5. Chung EY, Kim BH, Hong JT, Lee CK, Ahn B, Nam SY, Han SB and Kim Y. 2011. Resveratrol down-regulates interferon-$\gamma$-inducible inflammatory genes in macrophages: molecular mechanism via decreased STAT-1 activation. J Nutr Biochem 22, 902-909. https://doi.org/10.1016/j.jnutbio.2010.07.012
  6. D'Acquisto F, Iuvone T, Rombola L, Sautebin L, Di Rosa M and Carnuccio R. 1997. Involvement of $NF-{\kappa}B$ in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages. FEBS Lett 418, 175-178. https://doi.org/10.1016/S0014-5793(97)01377-X
  7. Dinarello CA. 1999. Cytokines as endogenous pyrogens. J Infect Dis 179(Suppl 2), S294-S304. https://doi.org/10.1086/513856
  8. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB and Lipsky PE. 1998. Cyclooxygenase in biology and disease. FASEB J 12, 1063-1073.
  9. Ganesan P, Kumar CS and Bhaskar N. 2008. Antioxidant properties of methanol extract and its solvent fractions obtained from selected Indian red seaweeds. Bioresour Technol 99, 2717-2723. https://doi.org/10.1016/j.biortech.2007.07.005
  10. Guha M and Mackman N. 2001. LPS induction of gene expression in human monocytes. Cell Signal 13, 85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  11. Heo SJ, Yoon WJ, Kim KN, Ahn GN, Kang SM, Kang DH, Affan A, Oh C, Jung WK and Jeon YJ. 2010. Evaluation of anti-inflammatory effect of fucoxanthin isolated from brown algae in lipopolysaccharide-stimulated RAW 264.7 macrophages. Food Chem Toxicol 48, 2045-2051. https://doi.org/10.1016/j.fct.2010.05.003
  12. Jin M, Suh SJ, Yang JH, Lu Y, Kim SJ, Kwon S, Jo TH, Kim JW, Park YI, Ahn GW, Lee CK, Kim CH, Son JK, Son KH and Chang HW. 2010. Anti-inflammatory activity of bark of Dioscorea batatas DECNE through the inhibition of iNOS and COX-2 expressions in RAW 264.7 cells via $NF-{\kappa}B$ and ERK1/2 inactivation. Food Chem Toxicol 48, 3073-3079. https://doi.org/10.1016/j.fct.2010.07.048
  13. Jung WK, Ahn YW, Lee SH, Choi YH, Kim SK, Yea SS, Choi I, Park SG, Seo SK, Lee SW and Choi IW. 2009. Ecklonia cava ethanolic extracts inhibit lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2 microglia via the MAP kinase and $NF-{\kappa}B$ pathways. Food Chem Toxicol 47, 410-417. https://doi.org/10.1016/j.fct.2008.11.041
  14. Kim AR, Shin TS, Lee MS, Park JY, Park KE, Yoon NY, Kim JS, Choi JS, Jang BC, Byun DS, Park NK and Kim HR. 2009. Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties. J Agric Food Chem 57, 3483-3489. https://doi.org/10.1021/jf900820x
  15. Kim AR, Lee MS, Shin TS, Hua H, Jang BC, Choi JS, Byun DS, Utsuki T, Ingram D and Kim HR. 2011. Phlorofucofuroeckol A inhibits the LPS-stimulated iNOS and COX-2 expressions in macrophages via inhibition of $NF-{\kappa}B$, Akt, and p38 MAPK. Toxicol In Vitro 25, 1789-1795. https://doi.org/10.1016/j.tiv.2011.09.012
  16. Kim EY and Moudgil KD. 2008. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunol Lett 120, 1-5. https://doi.org/10.1016/j.imlet.2008.07.008
  17. Kim MM and Kim SK. 2010. Effect of phloroglucinol on oxidative stress and inflammation. Food Chem Toxicol 48, 2925-2933. https://doi.org/10.1016/j.fct.2010.07.029
  18. Kim YC, An RB, Yoon NY, Nam TJ and Choi JS. 2005. Hepatoprotective constituents of the edible brown alga Ecklonia stolonifera on tacrine-induced cytotoxicity in Hep G2 cells. Arch Pharm Res 28, 1376-1380. https://doi.org/10.1007/BF02977904
  19. Lebovic DI, Bentzien F, Chao VA, Garrett EN, Meng YG and Taylor RN. 2000. Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1$\beta$. Mol Hum Reprod 6, 269-275. https://doi.org/10.1093/molehr/6.3.269
  20. Li Q and Verma IM. 2002. $NF-{\kappa}B$ regulation in the immune system. Nat Rev Immunol 2, 725-734. https://doi.org/10.1038/nri910
  21. Libby P. 2006. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 83, 456S-460S.
  22. Lopez A, Rico M, Rivero A and de Tangil MS. 2011. The effects of solvents on the phenolic contents and antioxidant activity of Stypocaulon scoparium algae extracts. Food Chem 125, 1104-1109. https://doi.org/10.1016/j.foodchem.2010.09.101
  23. Makarov SS. 2001. $NF-{\kappa}B$ in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res 3, 200-206. https://doi.org/10.1186/ar300
  24. Marks-Konczalik J, Chu SC and Moss J. 1998. Cytokine-mediated transcriptional induction of the human inducible nitric oxide synited thase gene requires both activator protein 1 and nuclear factor ${\kappa}B$ -binding sites. J Biol Chem 273, 22201-22208. https://doi.org/10.1074/jbc.273.35.22201
  25. Nathan C. 1992. Nitric oxide as a secretory product of mammalian cells. FASEB J 6, 3051-3064.
  26. Packard RR and Libby P. 2008. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 54, 24-38.
  27. Pan MH, Hong HM, Lin CL, Jhang AZ, Tsai JH, Badmaev V, Nagabhushanam K, Ho CT and Chen WJ. 2011. Se-methylselenocysteine inhibits lipopolysaccharide-induced $NF-{\kappa}B$ activation and iNOS induction in RAW 264.7 murine macrophages. Mol Nutr Food Res 55, 723-732. https://doi.org/10.1002/mnfr.201000481
  28. Pinelo M, Rubilar M, Sineiro J and Nunez MJ. 2004. Extraction of antioxidant phenolics from almond hulls (Prunus amygdalus) and pine sawdust (Pinus pinaster). Food Chem 85, 267-273. https://doi.org/10.1016/j.foodchem.2003.06.020
  29. Rahman I, Biswas SK and Kirkham PA. 2006. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol 72, 1439-1452. https://doi.org/10.1016/j.bcp.2006.07.004
  30. Shin JS, Park YM, Choi JH, Park HJ, Shin MC, Lee YS and Lee KT. 2010. Sulfuretin isolated from heartwood of Rhus verniciflua inhibits LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines expression via the downregulation of $NF-{\kappa}B$ in RAW 264.7 murine macrophage cells. Int Immunopharmacol 10, 943-950. https://doi.org/10.1016/j.intimp.2010.05.007
  31. Solinas G, Marchesi F, Garlanda C, Mantovani A and Allavena P. 2010. Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev 29, 243-248. https://doi.org/10.1007/s10555-010-9227-2
  32. Vane JR, Mitchell JA, Appleton I, Tomlinson A, Bishop-Bailey D, Croxtall J and Willoughby DA. 1994. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc Natl Acad Sci U S A 91, 2046-2050. https://doi.org/10.1073/pnas.91.6.2046
  33. Woo MN, Jeon SM, Shin YC, Lee MK, Kang MA and Choi MS. 2009. Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes and uncoupling proteins of visceral adipose tissue in mice. Mol Nutr Food Res 53, 1603-1611. https://doi.org/10.1002/mnfr.200900079
  34. Xie QW, Whisnant R and Nathan C. 1993. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon $\gamma$ and bacterial lipopolysaccharide. J Exp Med 177, 1779-1784. https://doi.org/10.1084/jem.177.6.1779
  35. Yoshimura A. 2006. Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97, 439-447. https://doi.org/10.1111/j.1349-7006.2006.00197.x
  36. Zhang G and Ghosh S. 2000. Molecular mechanisms of $NF-{\kappa}B$ activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res 6, 453-457.