The interaction between epithelial cells and microorganisms is the most important step in bacterial infections. Actinobacillus actinomycetemcomitans was suggested to play a significant role in the initiation of periodontitis because of its bacteriological characteristics. Prostaglandins (PG) mediate the inflammatory response. Human β-defensin-2 (hBD-2) is an antimicrobial peptide and contributes to innate immunity. E-cadherin is responsible for an epithelial intercellular junction. In this study, we investigated the syntheses of PGE2 and E-cadherin and the expression of hBD-2 in human gingival epithelial cells (HGEC) following exposure to A. actinomycetemcomitans. The levels of PGE2 and cyclooxygenase-2, which are responsible for an increase in PGE2, were increased depending on bacteria exposure time. hBD-2 mRNA was induced by A. actinomycetemcomitans, while HGEC exposed to A. actinomycetemcomitans showed a decrease in E-cadherin levels. Etodolac, a selective cyclooxygenase-2 inhibitor reinforced the increase in hBD-2 mRNA levels by A. actinomycetemcomitans. Furthermore, the etodolac suppressed the decrease in E-cadherin levels. Thus, endogenous PGE2 is involved in the hBD-2 and E-cadherin responses of HGEC to A. actinomycetemcomitans. These findings suggest that the inflammatory and antimicrobial response of gingival epithelial cells to A. actinomycetemcomitans is involved in the initiation of periodontal inflammation. A. actinomycetemcomitans may destroy the mechanical epithelial barrier by destroying E-cadherin.
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Fleiszig, S. M., D. J. Evans, N. Do, V. Vallas, S. Shin and K. E. Mostov. 1997. Epithelial cell polarity affects susceptibility to Pseudomonas aeruginosa invasion and cytotoxicity. Infect. Immun. 65:2861–2867.
Katz, J., V. Sambandam, J. H. Wu, S. M. Michalek, and D. F. Balkovetz. 2000. Characterization of Porphyromonas gingivalis-induced degradation of epithelial cell junctional complexes. Infect. Immun. 68:1441–1449.
Harder, J., J. Bartels, E. Christophers, and J. M. Schroder. 1997. A peptide antibiotic from human skin. Nature 387:861.
O'Neil, D. A., S. P. Cole, E. Martin-Porter, M. P. Housley, L. Liu, T. Ganz and M. F. Kagnoff. 2000. Regulation of human β-defensins by gastric epithelial cells in response to infection with Helicobacter pylori or stimulation with interleukin-1. Infect. Immun. 68:5412–5415.
Hamanaka, Y., M. Nakashima, A. Wada, M. Ito, H. Kurazono, H. Hojo, Y. Nakahara, S. Kohno, T. Hirayama, and I. Sekine. 2001. Expression of human β-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: Antibacterial effect of hBD-2 against Helicobacter pylori. Gut 49:481–487.
Krisanaprakornkit, S., J. R. Kimball, A. Weinberg, R. P. Darveau, B. W. Bainbridge, and B. A. Dale. 2000. Inducible expression of human β-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: Multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect. Immun. 68:2907–2915.
O'Neil, D. A., E. M. Porter, D. Elewaut, G. M. Anderson, L. Eckmann, T. Ganz, and M. F. Kagnoff. 1999. Expression and regulation of the human β-defensins hBD-1 and hBD-2 in intestinal epithelium. J. Immunol. 163(12):6718–6724.
Schröder, J. M. and J. Harder. 1999. Human beta-defensin-2. Int. J. Biochem. Cell Biol. 31:645–651.
Uchida, Y., H. Shiba, H. Komatsuzawa, T. Takemoto, M. Sakata, T. Fujita, H. Kawaguchi, M. Sugai, and H. Kurihara. 2001. Expression of IL-1β and IL-8 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans. Cytokine 14:152–161.
Yumoto, H., H. Nakae, M. Yamada, K. Fujinaka, C. Shinohara, S. Ebisu and T. Matsuo. 2001. Soluble products from Eikenella corrodens stimulate oral epithelial cells to induce inflammatory mediators. Oral Microbiol. Immunol. 16:296–305.
Laurent, F., M. F. Kagnoff, T. C. Savidge, M. Naciri, and L. Eckmann. 1998. Human intestinal epithelial cells respond to Cryptosporidium parvum infection with increased prostaglandin H synthase 2 expression and prostaglandin E2 and F2α production. Infect. Immun. 66:1787–1790.
Wang, B., N. Ruiz, A. Pentland, and M. Caparon. 1997. Keratinocyte proinflammatory responses to adherent and nonadherent group A streptococci. Infect. Immun. 65:2119–2126.
Lin, C. H., I. H. Kuan, H. M. Lee, W. S. Lee, J. R. Sheu, Y. S. Ho, C. H. Wang, and H. P. Kuo. 2001. Induction of cyclooxygenase-2 protein by lipoteichoic acid from Staphylococcus aureus in human pulmonary epithelial cells: Involvement of a nuclear factor-κ-dependent pathway. Br. J. Pharmacol. 134:543–552.
Mendieta, C. F., C. M. Reeve, and J. C. Romero. 1985. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis. J. Periodontol. 56:44–47.
Tsai, C. C., Y. C. Hong, C. C. Chen, and Y. M. Wu. 1998. Measurement of prostaglandin E2 and leukotriene B4 in the gingival crevicular fluid. J. Dent. 26:97–103.
Yucel-Lindberg, T., H. Ahola, S. Nilsson, J. Carlstedt-Duke, and T. Modeer. 1995. Interleukin-1β induces expression of cyclooxygenase-2 mRNA in human gingival fibroblasts. Inflammation 19:549–560.
Scott, M. G. and R. E. Hancock. 2000. Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit. Rev. Immunol. 20:407–431.
Wheelock, M. J. and P. J. Jensen. 1992. Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin. J. Cell Biol. 117:415–425.
Rodriguez-Boulan, E. and W. J. Nelson. 1989. Morphogenesis of the polarized epithelial cell phenotype. Science 245:718–725.
Ye P., C. C. Chapple, R. K. Kumar, N. Hunter. 2000. Expression patterns of E-cadherin, involucrin, and connexin gap junction proteins in the lining epithelia of inflamed gingiva. J. Pathol. 192:58–66.
Obiso, R. J. Jr, A. O. Azghani, and T. D. Wilkins. 1997. The Bacteroides fragilis toxin fragilysin disrupts the paracellular barrier of epithelial cells. Infect. Immun. 65:1431–1439.
Wu, S., K. C. Lim, J. Huang, R. F. Saidi, and C. L. Sears. 1998. Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc. Natl. Acad. Sci. U.S.A. 95:14979–14984.
Wilson, M. and B. Henderson. 1995. Virulence factors of Actinobacillus actinomycetemcomitans relevant to the pathogenesis of inflammatory periodontal diseases. FEMS Microbiol. Rev. 17:365–379.
Meyer, D. H. and P. M. Fives-Taylor. 1997. The role of Actinobacillus actinomycetemcomitans in the pathogenesis of periodontal disease. Trends Microbiol. 5:224–228.
Fives-Taylor, P. M., D. H. Meyer, K. P. Mintz, C. Brissette. 1999. Virulence factors of Actinobacillus actinomycetemcomitans. Periodontol. 2000. 20:136–167.
Huang, G. T., S. K. Haake, J. W. Kim, and N. H. Park. 1998. Differential expression of interleukin-8 and intercellular adhesion molecule-1 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis infection. Oral Microbiol. Immunol. 13:301–309.
Sato, J. D., T. Kawamoto, and T. Okamoto. 1987. Cholesterol requirement of P3-X63-Ag8 and X63-Ag8.653 mouse myeloma cells for growth in vitro. J. Exp. Med. 165:1761–1766.
Myoken, Y., Y. Myoken, T. Okamoto, J. D. Sato, and K. Takada. 1995. Effect of fibroblast growth factor-1 on the three-dimensional growth and morphogenesis of human salivary gland epithelial cells embedded in collagen gels. In Vitro Cell. Dev. Biol. Anim. 31:84–86.
Yuspa, S. H. and C. C. Harris. 1974. Altered differentiation of mouse epidermal cells treated with retinyl acetate in vitro. Exp. Cell Res. 86:95–105.
Krisanaprakornkit, S., A. Weinberg, C. N. Perez, and B. A. Dale. 1998. Expression of the peptide antibiotic human β-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect. Immun. 66:4222–4228.
Kawamoto, T., H. Pan, W. Yan, H. Ishida, E. Usui, R. Oda, K. Nakamasu, M. Noshiro, Y. Kawashima-Ohya, M. Fujii, H. Shintani, Y. Okada, and Y. Kato. 1998. Expression of membrane-bound transferrin-like protein p97 on the cell surface of chondrocytes. Eur. J. Biochem. 256:503–509.
Thomas, P. S. 1980. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. U.S.A. 77:5201–5205.
Sakata, M., H. Shiba, H. Komatsuzawa, T. Fujita, Y. Uchida, H. Yoshino, T. Ogawa, H. Kawaguchi, and H. Kurihara. 2002. Osteoprotegegerin levels increased by interleukin-1β in human periodontal ligament cells are suppressed throught prostaglandin E2 synthesized de novo. Cytokine 18:133–139.
DeWitt, D. L. 1991. Prostaglandin endoperoxide synthase: Regulation of enzyme expression. Biochim. Biophys. Acta 1083:121–134.
Pentland, A. P. and Needleman, P. 1986. Modulation of keratinocyte proliferation in vitro by endogenous prostaglandin synthesis. J. Clin. Invest. 77:246–251.
Pentland, A. P., J. George, C. Moran, and P. Needleman. 1987. Cellular confluence determines injury-induced prostaglandin E2 synthesis by human keratinocyte cultures. Biochim. Biophys. Acta 919:71–78.
Rys-Sikora, K. E., R. L. Konger, J. W. Schoggins, R. Malaviya, and A. P. Pentland. 2000. Coordinate expression of secretory phospholipase A2 and cyclooxygenase-2 in activated human keratinocytes. Am. J. Physiol. Cell Physiol. 278:C822-C833.
Knudsen, P. J., C. A. Dinarello, and T. B. Strom. 1986. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J. Immunol. 137:3189–3194.
Baer, P. N. 1971. The case for periodontosis as a clinical entity. J. Periodontol. 42:516–520.
Ulevitch, R. J. and P. S. Tobias. 1995. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu. Rev. Immunol. 13:437–457.
Smith, J. J., S. M. Travis, E. P. Greenberg, and M. J. Welsh. 1996. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell. 85(2):229–236.
Frye, M., J. Bargon, and R. Gropp. 2001. Expression of human beta-defensin-1 promotes differentiation of keratinocytes. J. Mol. Med. 79:275–282.
Noda, M., Y. Tatsumi, M. Tomizawa, T. Takama, S. Mitsufuji, H. Sugihara, K. Kashima, and T. Hattori. 2002. Effects of etodolac, a selective cyclooxygenase-2 inhibitor, on the expression of E-cadherin-catenin complexes in gastrointestinal cell lines. J. Gastroenterol. 37:896–904.
Canny, G., O. Levy, G. T. Furuta, S. Narravula-Alipati, R. B. Sisson, C. N. Serhan, and S. P. Colgan. 2002. Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia. Proc. Natl. Acad. Sci. U.S.A. 99:3902–3907.
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Noguchi, T., Shiba, H., Komatsuzawa, H. et al. Syntheses of Prostaglandin E2 and E-Cadherin and Gene Expression of β-defensin-2 by Human Gingival Epithelial Cells in Response to Actinobacillus actinomycetemcomitans . Inflammation 27, 341–349 (2003). https://doi.org/10.1023/B:IFLA.0000006702.27906.e9
- Actinobacillus actinomycetemcomitans
- gingival epithelial cells
- prostaglandin E2