DOI QR코드

DOI QR Code

사람 치주인대세포에서 Lipopolysaccharide와 니코틴으로 유도된 iNOS와 COX-2 발현에 NFATc의 관여

이상임;유지수
Lee, Sang-Im;Yu, Ji-Su

  • 투고 : 2015.11.02
  • 심사 : 2015.11.11
  • 발행 : 2015.12.31

초록

숙주 면역 반응과 면역 체계는 치주 질환에 대한 개인의 감수성의 주요 원인이다. 세균 감염과 흡연은 치주 조직의 파괴의 원인과 진행에 관여하는 중요한 환경 위험 요인이다. 따라서, 본 연구는 사람 치주인대세포에서 LPS와 니코틴이 전염증성 사이토카인인 iNOS/COX-2의 발현과 NO/$PGE_2$ 생산에 미치는 영향을 알아보고 NFATc1가 어떤 기전으로 항염작용을 하는지 밝히고자 하였다. LPS와 니코틴을 처리한 사람 치주인대세포에서 iNOS/COX-2의 발현과 함께 NO/$PGE_2$ 생산은 증가되었다. NFATc1 inhibitor인 CsA는 LPS와 니코틴에 의해 유도되는 iNOS/COX-2의 발현과 함께 NO/$PGE_2$ 생산을 감소시켰다. 이러한 연구 결과로 볼 때, NFAT signaling pathway가 LPS와 니코틴에 의한 iNOS/COX-2의 발현을 조절하여 NO/$PGE_2$ 매개 염증에 대해 방어할 수 있다고 생각된다.

키워드

Lipopolysaccharides;NFATc transcription factors;Nicotine;Periodontitis

참고문헌

  1. McDevitt MJ, Wang HY, Knobelman C, et al.: Interleukin-1 genetic association with periodontitis in clinical practice. J Periodontol 71: 156-163, 2000. https://doi.org/10.1902/jop.2000.71.2.156
  2. Noguchi K, Ishikawa I: The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontol 2000 43: 85-101, 2007. https://doi.org/10.1111/j.1600-0757.2006.00170.x
  3. Xie Q, Nathan C: The high-output nitric oxide pathway: role and regulation. J Leukoc Biol 56: 576-582, 1994. https://doi.org/10.1002/jlb.56.5.576
  4. Lee SH, Soyoola E, Chanmugam P, et al.: Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem 267: 25934-25938, 1992.
  5. Hwang SJ, Kim YK, Yang SJ, Cho HJ: Influence of smoking on matrix metalloproteinase-9 in the gingival crevicular fluid. J Dent Hyg Sci 11: 339-344, 2011.
  6. Zhong Y, Slade GD, Beck JD, Offenbacher S: Gingival crevicular fluid interleukin-$1{\beta}$, prostaglandin E2 and periodontal status in a community population. J Clin Periodontol 34: 285-293, 2007. https://doi.org/10.1111/j.1600-051X.2007.01057.x
  7. Cochran DL: Inflammation and bone loss in periodontal disease. J Periodontol 79: 1569-1576, 2008. https://doi.org/10.1902/jop.2008.080233
  8. Yamaji Y, Kubota T, Sasaguri K, Sato S, Suzuki Y, Kumada H: Inflammatory cytokine gene expression in human periodontal ligament fibroblasts treated with bacterial lipopolysaccharides. Infect Immun 63: 3576-3581, 1995.
  9. Park JY, Kim HS, Kook JK: Antimicrobial effect of (-)-epigalocatechin on Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. J Dent Hyg Sci 10: 161-165, 2010.
  10. Jonsson D, Nebel D, Bratthall G, Nilsson BO: The human periodontal ligament cell: a fibroblast-like cell acting as an immune cell. J Periodontal Res 46: 153-157, 2011. https://doi.org/10.1111/j.1600-0765.2010.01331.x
  11. Bregstrom J: Tobacco smoking and risk of periodontal disease. J Clin Periodontol 30: 107-13, 2003. https://doi.org/10.1034/j.1600-051X.2003.00272.x
  12. Johnson GK, Guthmiller JM: The impact of cigarette smoking on periodontal disease and treatment. Periodontol 2000 44: 178-194, 2007. https://doi.org/10.1111/j.1600-0757.2007.00212.x
  13. Cuff MJ, McQuade MJ, Scheidt MJ, Sutherland DE, Van Dyke TE: The presence of nicotine on root surfaces of periodontally diseased teeth in smokers. J Periodontol 60: 564-569, 1989. https://doi.org/10.1902/jop.1989.60.10.564
  14. McGuire JR, McQuade MJ, Rossmann JA, et al.: Nicotine in saliva and gingival crevicular fluid of smokers with periodontal disease. J Periodontol 60:176-181, 1989. https://doi.org/10.1902/jop.1989.60.4.176
  15. Shaw JP, Utz PJ, Durand DB, Toole JJ, Emmel EA, Crabtree GR: Identification of a putative regulator of early T-cell activation genes. Science 241: 202-205, 1988. https://doi.org/10.1126/science.3260404
  16. de la Pompa JL, Timmerman LA, Takimoto H, et al.: Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature 392: 182-186, 1998. https://doi.org/10.1038/32419
  17. Mercurio AM, Rabinovitz I: Towards a mechanistic understanding of tumor invasion-lessons from the ${\alpha}$6${\beta}$4 integrin Semin. Cancer Biol 11: 129-141, 2001. https://doi.org/10.1006/scbi.2000.0364
  18. Plyte S, Boncristiano M, Fattori E, et al.: Identification and characterization of a novel nuclear factor of activated T-cells-1 isoform expressed in mouse brain. J Biol Chem 276: 14350-14358, 2001. https://doi.org/10.1074/jbc.M007854200
  19. Rinne A, Banach K, Blatter LA: Regulation of nuclear factor of activated T cells (NFAT) in vascular endothelial cells. J Mol Cell Cardiol 47: 400-410, 2009. https://doi.org/10.1016/j.yjmcc.2009.06.010
  20. Nilsson LM, Nilsson-Ohman J, Zetterqvist AV, Gomez MF: Nuclear factor of activated T-cells transcription factors in the vasculature: the good guys or the bad guys? Curr Opin Lipidol 19: 483-490, 2008. https://doi.org/10.1097/MOL.0b013e32830dd545
  21. Kitagawa M, Kudo Y, Iizuka S, et al.: Effect of F-spondin on cementoblastic differentiation of human periodontal ligament cells. Biochem Biophys Res Commun 349: 1050-1056, 2006. https://doi.org/10.1016/j.bbrc.2006.08.142
  22. Chang YC, Hsieh YS, Lii CK, Huang FM, Tai KW, Chou MY: Induction of cfos expression by nicotine in human periodontal ligament fibroblasts is related to cellular thiol levels. J Periodontal Res 38: 44-50, 2003. https://doi.org/10.1034/j.1600-0765.2003.01642.x
  23. Chang YC, Tsai CH, Yang SH, Liu CM, Chou MY: Induction of cyclooxygenase-2 mRNA and protein expression in human gingival fibroblasts stimulated with nicotine. J Periodontal Res 38: 496-501, 2003. https://doi.org/10.1034/j.1600-0765.2003.00681.x
  24. Chang YC, Lai CC, Lin LF, Ni WF, Tsai CH: The upregulation of heme oxygenase-1 expression in human gingival fibroblasts stimulated with nicotine. J Periodontal Res 40: 252-257, 2005. https://doi.org/10.1111/j.1600-0765.2005.00804.x
  25. Choi JI, Nakagawa T, Yamada S, Takazoe I, Okuda K: Clinical, microbiological and immunological studies on recurrent periodontal disease. J Clin Periodontol 17: 426-434, 1990. https://doi.org/10.1111/j.1600-051X.1990.tb02341.x
  26. Yamaji Y, Kubota T, Sasaguri K, et al.: Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides. Infect Immun 63: 3576-3581, 1995.
  27. Chang YC, Yang SF, Lai CC, Liu JY, Hsieh YS: Regulation of matrix metalloproteinase production by cytokines, pharmacological agents and periodontal ligament fibroblast cultures. J Periodont Res 37: 196-203, 2002. https://doi.org/10.1034/j.1600-0765.2002.00663.x
  28. Jeong GS, Lee SH, Jeong SN, Kim YC, Kim EC: Antiinflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1. Int Immunopharmacol 12: 1374-1380, 2009.
  29. Katono T, Kawato T, Tanabe N, et al.: Effects of nicotine and lipopolysaccharide on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in human osteoblasts. Arch Oral Biol 54: 146-155, 2009. https://doi.org/10.1016/j.archoralbio.2008.09.017
  30. Arron JR, Winslow MM, Polleri A, et al.: NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441: 595-600, 2006. https://doi.org/10.1038/nature04678
  31. Beals CR, Clipstone NA, Ho SN, Crabtree GR: Nuclear localization of NF-ATc by a calcineurin-dependent, cyclosporinsensitive intramolecular interaction. Genes Dev 11: 824-834, 1997. https://doi.org/10.1101/gad.11.7.824
  32. Graef IA, Chen F, Crabtree GR: NFAT signaling in vertebrate development. Curr Opin Genet Dev 11: 505-512, 2001. https://doi.org/10.1016/S0959-437X(00)00225-2
  33. Mancini M, Toker A: NFAT proteins: emerging roles in cancer progression. Nat Rev Cancer 9: 810-820, 2009. https://doi.org/10.1038/nrc2735
  34. Graef IA, Chen F, Chen L, KuoA, Crabtree GR: Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 105: 863-875, 2001. https://doi.org/10.1016/S0092-8674(01)00396-8
  35. Graef IA, Wang F, Charron F, et al.: Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 113: 657-670, 2003. https://doi.org/10.1016/S0092-8674(03)00390-8
  36. Takayanagi H: The role of NFAT in osteoclast formation. Ann NY Acad Sci 1116: 227-237, 2007. https://doi.org/10.1196/annals.1402.071
  37. Koga T, Matsui Y, Asagiri M, et al.: NFAT and Osterix cooperatively regulate bone formation. Nat Med 11: 880-885, 2005. https://doi.org/10.1038/nm1270
  38. Lee SI: The role of NFATc1 on osteoblastic differentiation in human periodontal ligament cells. J Dent Hyg Sci 15: 488-494, 2015. https://doi.org/10.17135/jdhs.2015.15.4.488
  39. Orcel P, Bielakoff J, Modrowski D, Miravet L, de Vernejoul MC: Cyclosporin A induces in vivo inhibition of resorption and stimulation of formation in rat bone. J Bone Miner Res 4: 387-391, 1989
  40. Mena MP, Papiewska-Pajak I, Przygodzka P, et al.: NFAT2 regulates COX-2 expression and modulates the integrin repertoire in endothelial cells at the crossroads of angiogenesis and inflammation. Exp Cell Res 324: 124-136, 2014. https://doi.org/10.1016/j.yexcr.2014.03.008

과제정보

연구 과제 주관 기관 : National Research Foundation of Korea(NRF)