Variable Cell Responses to P. gingivalis Lipopolysaccharide

Abstract

Porphyromonas gingivalis is a major etiological agent of chronic periodontal diseases, the virulence of which has been attributed to different factors, including lipopolysaccharide (LPS). We investigated the differential responses induced by P. gingivalis LPS stimulation of human umbilical vein endothelial cells and human oral epithelial cells. RT-PCR analysis showed that P. gingivalis LPS used Toll-like receptor 2 (TLR2) to activate epithelial cells and Toll-like receptor 4 (TLR4) to activate endothelial cells. Both cell types were stimulated by P. gingivalis LPS to produce pro-inflammatory cytokines. Cytokine Array assay showed that although patterns of cytokine expression were similar in both cell types, some cytokines were specifically secreted by the endothelial cells, and others were specific to epithelial cells. These results support the idea that the same LPS preparation can act as a TLR2 or TLR4 agonist, depending on TLR expression of the host cell, inducing cytokine profiles that differ according to the cell type.

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References

Asai Y, Makimura Y, Kawabata A, Ogawa T -2007-. Soluble CD14 discriminates slight structural differences between lipid As that lead to distinct host cell activation. J Immunol 179:7674–7683.

Beutler B -2002-. Toll-like receptors: how they work and what they do. Curr Opin Hematol 9:2–10.

Da Silva Correia J, Soldau K, Christen U, Tobias S, Ulevitch RJ -2001-. Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. Transfer from CD14 to TLR4 and MD-2. J Biol Chem 276:21129–21135.

Darveau RP, Tanner A, Page RC -1997-. The microbial challenge in periodontitis. Periodontol 2000 14:12–32.

Darveau RP, Pham TT, Lemley K, Reife RA, Bainbridge BW, Coats SR, et al. -2004-. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both Toll-like receptors 2 and 4. Infect Immun 72:5041–5051.

Dziarski R, Wang Q, Miyake K, Kirschning CJ, Gupta D -2001-. MD-2 enables Toll-like receptor 2 -TLR2--mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components. J Immunol 166:1938–1944.

Elkaim R, Dahan M, Kocgozlu L, Werner S, Kanter D, Kretz JG, et al. -2008-. Prevalence of periodontal pathogens in subgingival lesions, atherosclerotic plaques and healthy blood vessels: a preliminary study. J Periodontal Res 43:224–231.

Gabay C, Kushner I -1999-. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454.

Gibson FC 3rd, Hong C, Chou HH, Yumoto H, Chen J, Lien E, et al -2004-. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation 109:2801–2806.

10.

Graves DT, Cochran D -2003-. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 74:391–401.

11.

Hajishengallis G, Tapping RI, Harokopakis E, Nishiyama S, Ratti P, Schifferle RE, et al. -2006-. Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus. Cell Microbiol 8:1557–1570.

12.

Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ -2000-. Identification of periodontal pathogens in atheromatous plaques. J Periodontol 71:1554–1560.

13.

Hashimoto M, Asai Y, Ogawa T -2004-. Separation and structural analysis of lipoprotein in a lipopolysaccharide preparation from Porphyromonas gingivalis. Int Immunol 16:1431–1437.

14.

Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ -2000-. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine Toll-like receptor 2. J Immunol 165:618–622.

15.

Hirschfeld M, Weiss JJ, Toshchakov V, Salkowski CA, Cody MJ, Ward DC, et al. -2001-. Signaling by Toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun 69:1477–1482.

16.

Kumada H, Haishima Y, Watanabe K, Hasegawa C, Tsuchiya T, Tanamoto K, et al. -2008-. Biological properties of the native and synthetic lipid A of Porphyromonas gingivalis lipopolysaccharide. Oral Microbiol Immunol 23:60–69.

17.

Lusis AJ -2000-. Atherosclerosis. Nature 407:233–241.

18.

Nassar H, Chou HH, Khlgatian M, Gibson FC 3rd, Van Dyke TE, Genco CA -2002-. Role for fimbriae and lysine-specific cysteine proteinase gingi-pain K in expression of interleukin-8 and monocyte chemoattractant protein in Porphyromonas gingivalis-infected endothelial cells. Infect Immun 70:268–276.

19.

Reife RA, Coats SR, Al-Qutub M, Dixon DM, Braham PA, Billharz RJ, et al. -2006-. Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition. Cell Microbiol 8:857–868.

20.

Sandros J, Karlsson C, Lappin DF, Madianos PN, Kinane DF, Papapanou PN -2000-. Cytokine responses of oral epithelial cells to Porphyromonas gingivalis infection. J Dent Res 79:1808–1814.

21.

Scannapieco FA, Bush RB, Paju S -2003-. Associations between periodontal disease and risk for atherosclerosis, cardiovascular disease, and stroke. A systematic review. Ann Periodontol 8:38–53.

22.

Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, et al. -1990-. Structure and function of lipopolysaccharide binding protein. Science 249:1429–1431.

23.

Socransky SS, Haffajee AD -1992-. The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol 63:322–331.

24.

Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al. -1999-. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11:443–451.

25.

Wang PL, Ohura K -2002-. Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts—CD14 and Toll-like receptors. Crit Rev Oral Biol Med 13:132–142.

26.

Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC -1990-. CD14 a receptor for complexes of lipopolysaccharide -LPS- and LPS binding protein. Science 249:1431–1433.

27.

Zhang D, Chen L, Li S, Gu Z, Yan J -2008-. Lipopolysaccharide -LPS- of Porphyromonas gingivalis induces IL-1beta, TNF-alpha and IL-6 production by THP-1 cells in a way different from that of Escherichia coli LPS. Innate Immun 14:99–107.

28.

Zhou Q, Desta T, Fenton M, Graves DT, Amar S -2005-. Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein. Infect Immun 73:935–943; erratum in Infect Immun 74:1995, 2006.

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