This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-H. Articles by Choi, B.-K. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-H. Articles by Choi, B.-K.

Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum, the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

Department of Oromaxillofacial Infection and Immunity,¹ Dental Research Institute, College of Dentistry, Seoul National University, Seoul, Republic of Korea²

Received 14 July 2004/ Returned for modification 13 August 2004/ Accepted 27 September 2004

Treponema maltophilum and Treponema lecithinolyticum belong to the group IV oral spirochetes and are associated with endodontic infections, as well as periodontitis. Recently, the genes encoding the major surface proteins (Msps) of these bacteria (MspA and MspTL, respectively) were cloned and sequenced. The amino acid sequences of these proteins showed significant similarity. In this study we analyzed the functional role of these homologous proteins in human monocytic THP-1 cells and primary cultured periodontal ligament (PDL) cells using recombinant proteins. The complete genes encoding MspA and MspTL without the signal sequence were cloned into Escherichia coli by using the expression vector pQE-30. Fusion proteins tagged with N-terminal hexahistidine (recombinant MspA [rMspA] and rMspTL) were obtained, and any possible contamination of the recombinant proteins with E. coli endotoxin was removed by using polymyxin B-agarose. Flow cytometry showed that rMspA and rMspTL upregulated the expression of intercellular adhesion molecule 1 (ICAM-1) in both THP-1 and PDL cells. Expression of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, was also induced significantly in both cell types by the Msps, as determined by reverse transcription-PCR and an enzyme-linked immunosorbent assay, whereas IL-1ß synthesis could be detected only in the THP-1 cells. The upregulation of ICAM-1, IL-6, and IL-8 was completely inhibited by pretreating the cells with an NF-B activation inhibitor, L-1-tosylamido-2-phenylethyl chloromethyl ketone. This suggests involvement of NF-B activation. The increased ICAM-1 and IL-8 expression in the THP-1 cells obtained with rMsps was not inhibited in the presence of the IL-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1. Our results show that the Msps of the group IV oral spirochetes may play an important role in amplifying the local immune response by continuous inflammatory cell recruitment and retention at an infection site by stimulation of expression of ICAM-1 and proinflammatory cytokines.

Editor: J. T. Barbieri

This article has been cited by other articles:

• Jun, H.-K., Kang, Y.-M., Lee, H.-R., Lee, S.-H., Choi, B.-K. (2008). Highly Conserved Surface Proteins of Oral Spirochetes as Adhesins and Potent Inducers of Proinflammatory and Osteoclastogenic Factors. Infect. Immun. 76: 2428-2438 [Abstract] [Full Text]  
• Jun, H.-K., Lee, H.-R., Lee, S.-H., Choi, B.-K. (2007). Mapping of the proinflammatory domains of MspTL of Treponema lecithinolyticum. Microbiology 153: 2386-2392 [Abstract] [Full Text]  
• Verstappen, J., Von den Hoff, J.W. (2006). Tissue Inhibitors of Metalloproteinases (TIMPs): Their Biological Functions and Involvement in Oral Disease.. J. Dent. Res. 85: 1074-1084 [Abstract] [Full Text]  
• Moter, A., Riep, B., Haban, V., Heuner, K., Siebert, G., Berning, M., Wyss, C., Ehmke, B., Flemmig, T. F., Gobel, U. B. (2006). Molecular epidemiology of oral treponemes in patients with periodontitis and in periodontitis-resistant subjects.. J. Clin. Microbiol. 44: 3078-3085 [Abstract] [Full Text]  
• Lee, S.-H., Kim, K.-K., Rhyu, I.-C., Koh, S., Lee, D.-S., Choi, B.-K. (2006). Phenol/water extract of Treponema socranskii subsp. socranskii as an antagonist of Toll-like receptor 4 signalling. Microbiology 152: 535-546 [Abstract] [Full Text]