Document Detail


Treponema denticola immunoinhibitory protein induces irreversible G1 arrest in activated human lymphocytes.
MedLine Citation:
PMID:  15107064     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oral spirochetes may contribute to the pathogenesis of a number of disorders including periodontal and periradicular diseases; however, the mechanism (s) by which these organisms act to cause disease is unknown. We have previously shown that extracts of the oral spirochete, Treponema denticola, contain an immunosuppressive protein (Sip) which impairs human lymphocyte proliferation. The objective of this study was to determine the mechanism by which Sip alters the proliferative response of lymphocytes. Human T-cells were activated by PHA in the presence or absence of Sip and cell cycle progression was assessed by flow cytometry. Cell cycle distribution was based upon DNA, RNA and protein content as well as expression of the activation markers; CD69 and IL-2R. Seventy-two hours following activation with PHA, cells were found in the G0, G1, S and G2/M phases of the cell cycle. In contrast, pretreatment with Sip resulted in a significant reduction of cells in the S and G2/M phases and a concomitant increase in the G1 phase. Sip did not alter the expression of the early activation markers CD69 and CD25R. To determine if G1 arrest resulted in activation of the checkpoint and cell death, we also monitored Sip-treated cells for apoptosis. Indeed, treatment with Sip resulted in both DNA fragmentation and caspase activation after 96 h. Our results indicate that Sip induces G1 arrest in human T-cells and, furthermore, that the arrest is irreversible, culminating in activation of the apoptotic cascade. We propose that if cell cycle arrest occurs in vivo, it may result in local and/or systemic immunosuppression and thereby enhance the pathogenicity of spirochetes and/or that of other opportunistic organisms.
Authors:
W Lee; L Pankoski; A Zekavat; B J Shenker
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oral microbiology and immunology     Volume:  19     ISSN:  0902-0055     ISO Abbreviation:  Oral Microbiol. Immunol.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-04-26     Completed Date:  2004-06-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8707451     Medline TA:  Oral Microbiol Immunol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  144-9     Citation Subset:  D    
Copyright Information:
Copyright Blackwell Munksgaard, 2004.
Affiliation:
Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104-6030, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / analysis
Antigens, Differentiation, T-Lymphocyte / analysis
Apoptosis / immunology
Bacterial Proteins / immunology*
Caspases / analysis
Cell Death / immunology
DNA Damage
Flow Cytometry
G1 Phase / immunology
Glycoproteins / immunology*
Humans
Immune Tolerance / immunology
Lymphocyte Activation / immunology*
Mitogens / pharmacology
Opportunistic Infections / immunology
Phytohemagglutinins / pharmacology
Receptors, Interleukin-2 / analysis
T-Lymphocytes / immunology*
Treponema / immunology*,  pathogenicity
Treponemal Infections / immunology
Grant Support
ID/Acronym/Agency:
DE14191/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation, T-Lymphocyte; 0/Bacterial Proteins; 0/CD69 antigen; 0/Glycoproteins; 0/Mitogens; 0/Phytohemagglutinins; 0/Receptors, Interleukin-2; 0/serum immunosuppressive factor, human; EC 3.4.22.-/Caspases

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