FEMALE SEX HORMONES DECREASE MMP-1 AND MMP-8 EXPRESSIONS IN Porphyromonas gingivalis LPS-STIMULATED HUMAN GINGIVAL FIBROBLASTS
Keywords:
Sex hormones, gingival fibroblasts, MMPs, inflammationAbstract
Elevated female sex hormone concentrations are associated with gingival inflammation during pregnancy. This study aimed to investigate the effects of female sex hormones and Porphyromonas gingivalis lipopolysaccharide (LPS) on the expression of matrix metalloproteinase (MMP)-1 and MMP-8 in human gingival fibroblasts, in vitro. Primary cultures of human gingival fibroblasts (HGFs) were incubated with β-estradiol (0.1-10μg/ml), or progesterone (1-100 μg/ml), or LPS from P. gingivalis (0.1-10 μg/ml) for up to48 h. The cell viability of HGFs was examined by cell proliferation assay. The expression of MMP-1 and MMP-8 was investigated using conventional and real-time reverse transcription polymerase chain reaction (RT-PCR). Β-estradiol (0.1-10 μg/ml) and progesterone (1-100 μg/ml) did not alter the number of cells of HGFs after 24 h incubation.Stimulation of HGFs with LPS from P. gingivalis up-regulated the expression of MMP-1and MMP-8, whereas β-estradiol and progesterone inhibited both MMP-1 and MMP-8expression. Pre-treatment of gingival fibroblasts with either estrogen or progesterone decreased the effect of LPS from P. gingivalis on MMP-1 and MMP-8 expression by gingival fibroblasts. The effects of estrogen and progesterone on the expression of MMP-1and MMP-8 by human gingival fibroblasts may play a role in pregnancy gingivitis.
References
Armitage, G.C. (2013). Bi-directional relationshipbetween pregnancy and periodontal disease.Periodontol. 61:160-176.
Bozkurt, S.B., Hakki, S.S., Hakki, E.E., Durak, Y., andKantarci, A. (2017). Porphyromonas gingivalislipopolysaccharide induces a pro-inflammatoryhuman gingival fibroblast phenotype. Inflammation40:144-153.
Carrillo-de-Albornoz, A., Figuero, E., Herrera, D., Cuesta,P., and Bascones-Martinez, A. (2012). Gingivalchanges during pregnancy: III. Impact of clinical,microbiological, immunological and sociodemographicfactors on gingival inflammation. J.Clin. Periodontol., 39:272-283.
Cavalla, F., Hernández-Ríos, P., Sorsa, T., Biguetta, C.,and Hernández, M. (2017). Matrixmetalloproteinases as regulators of periodontalinflammation. Int. J. Mol. Sci., 18:440.
Christoffers, A.B., Kreisler, M., and Willershausen, B.(2003). Effects of estradiol and progesterone on theproliferation of human gingival fibroblasts. Eur. J.Med. Res., 8:535-542.
Edelstam, G., Karlsson, C., Westgren, M., Lowbeer, C.,and Swahn, M.L. (2007). Human chorionicgonadatropin (hCG) during third trimesterpregnancy. Scand. J. Clin. Lab. Inv., 67:519-525.
Figuero, E., Carrillo-de-Albornoz, A., Herrera, D., andBascones-Martinez, A. (2010). Gingival changesduring pregnancy: I. Influence of hormonalvariations on clinical and immunologicalparameters. J. Clin. Periodontol., 37:220-229.
Garcia-Gomez, E., Gonzalez-Pedrajo, B., and Camacho-Arroyo, I. (2013). Role of sex steroid hormones inbacterial-host interactions. Biomed ResearchInternational, 928290, 10p.
Giannoni, E., Guignard, L., Knaup Reymond, M., Perreau,M., Roth-Kleiner, M., Calandra, T., and Roger, T.(2011). Estradiol and progesterone strongly inhibitthe innate immune response of mononuclear cells innewborns. Infect. Immun., 79:2690-2698.
Gilliver, S.C. (2010). Sex steroids as inflammatoryregulators. J. Steroid Biochem., 120:105-115.Graves, D. (2008). Cytokines that promote periodontaltissue destruction. J. Periodontol., 79:1585-1591.
Gursoy, M., Gursoy, U.K., Sorsa, T., Pajukanta, R., andKononen, E. (2013). High salivary estrogen and riskof developing pregnancy gingivitis. J. Periodontol.,84:1281-1289.
Gursoy, M., Kononen, E., Gursoy, U.K., Tervahartiala, T.,Pajukanta, R., and Sorsa, T. (2010a). Periodontalstatus and neutrophilic enzyme levels in gingivalcrevicular fluid during pregnancy and postpartum.J. Periodontol., 81:1790-1796.
Gursoy, M., Kononen, E., Tervahartiala, T., Gursoy, U.K.,Pajukanta, R., and Sorsa, T. (2010b). Longitudinalstudy of salivary proteinases during pregnancy andpostpartum. J. Periodontal Res., 45:496-503.
Hajishengallis, G. (2015). Periodontitis: from microbialimmune subversion to systemic inflammation. Nat.Rev. Immunol., 15:30-44.
Herath, T.D.K., Wang, Y., Seneviratne, C.J., Darveau,R.P., Wang, C.Y., and Jin, L. (2013). Theexpression and regulation of matrixmetalloproteinase-3 is critically modulated byPorphyromonas gingivalis lipopolysaccharide withheterogeneous lipid A structures in human gingivalfibroblasts. BMC Microbiol., 13:73.
Jain, S.K., Kannan, K., and Prouty, L. (2004).Progesterone, but not 17beta-estradiol, increasesTNF-alpha secretion in U937 monocytes. Cytokine,26:102-105.
Jitprasertwong, P., Chaisomboon, N., and Jamdee, K.(2013). Progesterone, but not β-estradiol, enhancesPorphyromonas gingivalis lipopolysaccharideinducedvascular endothelial growth factor-Aexpression in human THP-1 monocytes. J. Dent.Sci., 8:358-364.
Jitprasertwong, P., Charadram, N., Kumphune, S.,Pongcharoen, S., and Sirisinha, S. (2016). Femalesex hormones modulate Porphyromonas gingivalislipopolysaccharide-induced toll-like receptorsignaling in primary human monocytes. J.Periodontal Res., 51:395-406.
Jitprasertwong, P., Jaedicke, K.M., Nile, C.J., Preshaw,P.M., and Taylor, J.J. (2014). Leptin enhances thesecretion of interleukin (IL)-18, but not IL-1beta,from human monocytes via activation of caspase-1.Cytokine, 65:222-230.
Jones, L.A., Kreem, S., Shweash, M., Paul, A., Alexander,J., and Roberts, C.W. (2010). Differentialmodulation of TLR3- and TLR4-mediated dendriticcell maturation and function by progesterone. J.Immunol., 185:4525-4534.
Kuo, P.J., Tu, H.P., Chin, Y.T., Lu, S.H., Chiang, C.Y.,Chen, R.Y., and Fu, E. (2012). Cyclosporine-Ainhibits MMP-2 and -9 activities in the presence ofPorphyromonas gingivalis lipopolysaccharide: anexperiment in human gingival fibroblast and U937macrophage co-culture. J. Periodontal Res., 47:431-438.
Lapp, C.A. and Lapp, D.F. (2005). Analysis of interleukinactivatedhuman gingival fibroblasts: modulation of chemokine responses by female hormones. J.Periodontol., 76:803-812.
Lapp, C.A., Lohse, J.E., Lewis, J.B., Dickinson, D.P.,Billman, M., Hanes, P.J., and Lapp, D.F. (2003).The effects of progesterone on matrixmetalloproteinases in cultured human gingivalfibroblasts. J. Periodontol., 74:277-288.
Mahanonda, R., Jitprasertwong, P., Sa-Ard-Iam, N.,Rerkyen, P., Charatkulangkun, O., Jansisyanont, P.,Nisapakultorn, K., Yongvanichit, K., andPichyangkul, S. (2008). Effects of IL-17 on humangingival fibroblasts. J. Dent. Res., 87:267-272.
Mariotti, A. and Mawhinney, M. (2013). Endocrinology ofsex steroid hormones and cell dynamics in theperiodontium. Periodontol., 61:69-88.
Mariotti, A.J. (2005). Estrogen and extracellular matrixinfluence human gingival fibroblast proliferationand protein production. J. Periodontol., 76:1391-1397.
Markou, E., Eleana, B., Lazaros, T., and Antonios, K.(2009). The influence of sex steroid hormones ongingiva of women. Open Dent. J., 3:114-119.
Mealey, B.L. and Moritz, A.J. (2003). Hormonalinfluences: effects of diabetes mellitus andendogenous female sex steroid hormones on theperiodontium. Periodontol., 32:59-81.
Morishita, M., Miyagi, M., and Iwamoto, Y. (1999).Effects of sex hormones on production ofinterleukin-1 by human peripheral monocytes. J.Periodontol., 70:757-760.
Nebel, D., Jonsson, D., Norderyd, O., Bratthall, G., andNilsson, B.O. (2010). Differential regulation ofchemokine expression by estrogen in humanperiodontal ligament cells. J. Periodontal Res.,45:796-802.
Raber-Durlacher, J.E., van Steenbergen, T.J., van derVelden, U., de Graaff, J., and Abraham-Inpijn, L.(1994). Experimental gingivitis during pregnancyand post-partum: clinical, endocrinological, andmicrobiological aspects. J. Clin. Periodontol.,21:549-558.
Sorsa, T., Tjaderhane, L., Konttinen, Y.T., Lauhio, A.,Salo, T., Lee, H.M., Golub, L.M., Brown, D.L., andMantyla, P. (2006). Matrix metalloproteinases:contribution to pathogenesis, diagnosis andtreatment of periodontal inflammation. Ann. Med.,38:306-321.
Stadler, A.F., Angst, P.D., Arce, R.M., Gomes, S.C.,Oppermann, R.V., and Susin, C. (2016). Gingivalcrevicular fluid levels of cytokines/chemokines inchronic periodontitis: a meta-analysis. J. Clin.Periodontol., 43:727-745.
Su, L., Sun, Y., Ma, F., Lu, P., Huang, H., and Zhou, J.(2009). Progesterone inhibits toll-like receptor 4-mediated innate immune response in macrophagesby suppressing NF-kappaB activation and enhancing SOCS1 expression. Immunol. Lett.,125:151-155.
Whitacre, C.C. (2001). Sex differences in autoimmune disease. Nat. Immunol., 2:777-780.
Yokoyama, M., Hinode, D., Masuda, K., Yoshioka, M.,and Grenier, D. (2005). Effect of female sexhormones on Campylobacter rectus and human gingival fibroblasts. Oral Microbiol. Immun.,20:239-243
