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NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells
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  • Journal title : Journal of dental hygiene science
  • Volume 15, Issue 6,  2015, pp.753-760
  • Publisher : the Korean Society of Dental Hygiene science
  • DOI : 10.17135/jdhs.2015.15.6.753
 Title & Authors
NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells
Lee, Sang-Im; Yu, Ji-Su;
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Although nuclear factor of activated T cell (NFAT) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of NFAT on the proinflammatory mediators activated by lipopolysaccharide (LPS) plus nicotine stimulation in human periodontal ligament cells (hPDLCs). The production of nitric oxide (NO) and prostaglandin was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NFAT proteins was evaluated by Western blot analysis. LPS plus nicotine synergistically induced the production of NO and and increased the protein expression of iNOS, COX-2 and NFAT. Treatment with an NFAT inhibitor blocked the LPS plus nicotine-stimulated NO and release as well as the expression of iNOS and COX-2. Our data suggest that the LPS plus nicotine-induced inflammatory effects on hPDLCs may act through a novel mechanism involving the action of NFAT. Thus, NFAT may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.
Lipopolysaccharides;NFATc transcription factors;Nicotine;Periodontitis;
 Cited by
McDevitt MJ, Wang HY, Knobelman C, et al.: Interleukin-1 genetic association with periodontitis in clinical practice. J Periodontol 71: 156-163, 2000. crossref(new window)

Noguchi K, Ishikawa I: The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontol 2000 43: 85-101, 2007. crossref(new window)

Xie Q, Nathan C: The high-output nitric oxide pathway: role and regulation. J Leukoc Biol 56: 576-582, 1994. crossref(new window)

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.

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.

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. crossref(new window)

Cochran DL: Inflammation and bone loss in periodontal disease. J Periodontol 79: 1569-1576, 2008. crossref(new window)

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.

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.

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. crossref(new window)

Bregstrom J: Tobacco smoking and risk of periodontal disease. J Clin Periodontol 30: 107-13, 2003. crossref(new window)

Johnson GK, Guthmiller JM: The impact of cigarette smoking on periodontal disease and treatment. Periodontol 2000 44: 178-194, 2007. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Graef IA, Chen F, Crabtree GR: NFAT signaling in vertebrate development. Curr Opin Genet Dev 11: 505-512, 2001. crossref(new window)

Mancini M, Toker A: NFAT proteins: emerging roles in cancer progression. Nat Rev Cancer 9: 810-820, 2009. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Takayanagi H: The role of NFAT in osteoclast formation. Ann NY Acad Sci 1116: 227-237, 2007. crossref(new window)

Koga T, Matsui Y, Asagiri M, et al.: NFAT and Osterix cooperatively regulate bone formation. Nat Med 11: 880-885, 2005. crossref(new window)

Lee SI: The role of NFATc1 on osteoblastic differentiation in human periodontal ligament cells. J Dent Hyg Sci 15: 488-494, 2015. crossref(new window)

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

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. crossref(new window)