Linked Life Data

19380831

Source:http://linkedlifedata.com/resource/pubmed/id/19380831

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-4-21
pubmed:abstractText
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-beta, 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-beta 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-beta and the IFN-stimulated genes IFN-gamma-inducible protein-10 (IP-10) and RANTES. A neutralizing anti-IFN-beta 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 IkappaB kinase (IKKi). MspTL also induced dimerization of IFN regulatory factor-3 (IRF-3) and translocation into the nucleus. The lipid rapid-disrupting agents methyl-beta-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-beta expression and subsequent up-regulation of IP-10 and RANTES via TBK1/IRF-3/STAT-1 signaling secondary to lipid raft activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5823-35
pubmed:meshHeading
pubmed-meshheading:19380831-Active Transport, Cell Nucleus, pubmed-meshheading:19380831-Bacterial Proteins, pubmed-meshheading:19380831-Cell Line, Tumor, pubmed-meshheading:19380831-Chemokine CCL5, pubmed-meshheading:19380831-Chemokine CXCL10, pubmed-meshheading:19380831-Dimerization, pubmed-meshheading:19380831-Fibroblasts, pubmed-meshheading:19380831-Gene Expression Regulation, Bacterial, pubmed-meshheading:19380831-Humans, pubmed-meshheading:19380831-Interferon Regulatory Factor-3, pubmed-meshheading:19380831-Interferon-beta, pubmed-meshheading:19380831-Membrane Microdomains, pubmed-meshheading:19380831-Monocytes, pubmed-meshheading:19380831-Periodontitis, pubmed-meshheading:19380831-Porins, pubmed-meshheading:19380831-Protein-Serine-Threonine Kinases, pubmed-meshheading:19380831-Signal Transduction, pubmed-meshheading:19380831-Treponema, pubmed-meshheading:19380831-Treponemal Infections, pubmed-meshheading:19380831-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
The major outer membrane protein of a periodontopathogen induces IFN-beta and IFN-stimulated genes in monocytes via lipid raft and TANK-binding kinase 1/IFN regulatory factor-3.
pubmed:affiliation
Department of Oral Microbiology and Immunology, Seoul National University, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't