| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Oral Microbiology and Immunology and
Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea; and
Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Surface molecules of pathogens play an important role in stimulating host immune responses. Elucidation of the signaling pathways activated by critical surface molecules in host cells provides insight into the molecular pathogenesis resulting from bacteria-host interactions. MspTL is the most abundant outer membrane protein of Treponema lecithinolyticum, which is associated with periodontitis, and induces expression of a variety of proinflammatory factors. Although bacteria and bacterial components like LPS and flagellin are known to induce IFN-β, induction by bacterial surface proteins has not been reported. In the present study, we investigated MspTL-mediated activation of signaling pathways stimulating up-regulation of IFN-β and IFN-stimulated genes in a human monocytic cell line, THP-1 cells, and primary cultured human gingival fibroblasts. MspTL treatment of the cells induced IFN-β and the IFN-stimulated genes IFN-
-inducible protein-10 (IP-10) and RANTES. A neutralizing anti-IFN-β Ab significantly reduced the expression of IP-10 and RANTES, as well as STAT-1 activation, which was also induced by MspTL. Experiments using specific small interfering RNA showed that MspTL activated TANK-binding kinase 1 (TBK1), but not inducible I
B kinase (IKKi). MspTL also induced dimerization of IFN regulatory factor-3 (IRF-3) and translocation into the nucleus. The lipid rapid-disrupting agents methyl-β-cyclodextrin, nystatin, and filipin inhibited the MspTL internalization and cellular responses, demonstrating that lipid raft activation was a prerequisite for MspTL cellular signaling. Our results demonstrate that MspTL, the major outer protein of T. lecithinolyticum, induced IFN-β expression and subsequent up-regulation of IP-10 and RANTES via TBK1/IRF-3/STAT-1 signaling secondary to lipid raft activation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Korea Research Foundation Grant funded by the Korean Government (Ministry of Education and Human Resource Development, Basic Research Promotion Fund) (KRF-2006-531-E00072). S.-H. L., H.-K. J., and H.-R. L. are recipients of a scholarship from the BK21 Program (Craniomaxillofacial Life Science 21).
2 Address correspondence and reprint requests to Dr. Bong-Kyu Choi, Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul 110-749, Republic of Korea. E-mail: bongchoi{at}snu.ac.kr
3 Abbreviations used in this paper: HGF, human gingival fibroblast; CHO, Chinese hamster ovary; CpG-ODN, CpG-oligodeoxynucleotide, unmethylated dsDNA; IKKi, inducible IB kinase; IP-10, IFN--inducible protein-10; IRF, IFN regulatory factor; ISG, IFN-stimulated gene; MβCD, methyl-β-cyclodextrin; MOI, multiplicity of infection; OM, outer membrane; Pam3CSK4, palmitoyl-3-cysteine-serine-lysine-4; PAMP, pathogen-associated molecular pattern; PDL, periodontal ligament cell; PDTC, pyrrolidine dithiocarbamate; siRNA, small interfering RNA; TBK1, TANK-binding kinase 1.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
