PMID- 19716548
OWN - NLM
STAT- MEDLINE
DCOM- 20100408
LR  - 20171116
IS  - 1879-1506 (Electronic)
IS  - 0003-9969 (Linking)
VI  - 54
IP  - 11
DP  - 2009 Nov
TI  - Activation of the extrinsic apoptotic pathway by TNF-alpha in human salivary 
      gland (HSG) cells in vitro, suggests a role for the TNF receptor (TNF-R) and 
      intercellular adhesion molecule-1 (ICAM-1) in Sjogren's syndrome-associated 
      autoimmune sialadenitis.
PG  - 986-96
LID - 10.1016/j.archoralbio.2009.07.011 [doi]
AB  - Studies suggest that apoptosis plays a major role in destruction of salivary 
      glands in Sjogren's syndrome. We hypothesise that apoptosis results in the 
      exposure of cryptic T cell epitopes and an autoimmune response which is 
      pathway-specific. OBJECTIVE: To activate the extrinsic or intrinsic apoptotic 
      pathway to examine morphology, adhesion molecules, markers of antigen processing, 
      and autoantigens on apoptotic bodies in vitro. METHODS: Tumor necrosis 
      factor-alpha (TNF-alpha) or staurosporine, a protein kinase inhibitor, was used 
      to trigger the extrinsic or intrinsic apoptotic pathway in a Human Salivary Gland 
      cell line (HSG), in vitro. Activated genes were profiled by cDNA array. Apoptotic 
      bodies were visualised using light and SEM. Proteins were evaluated by 
      immunofluorescence and confirmed by functional binding assays with Jurkat 
      lymphocytes. RESULTS: TNF-alpha-triggered extrinsic apoptosis resulted in 
      "sticky" aggregated, apoptotic bodies which displayed cleaved alpha-fodrin 
      autoantigen. In contrast, intrinsic apoptosis induced by staurosporine, resulted 
      in dispersed cell blebs which were alpha-fodrin-negative. cDNA arrays revealed 
      that TNF-alpha, but not staurosporine, upregulated transcriptional expression of 
      Intercellular Adhesion Molecule-1 (ICAM-1) and Macrophage Inflammatory Protein-3 
      (CCL20). CONCLUSION: The apoptotic pathway controls morphological, structural and 
      functional properties of apoptotic bodies. Collectively, TNF-alpha-dependent 
      activation of the extrinsic apoptotic pathway leads to upregulation of ICAM-1 and 
      CCL20 in HSG in vitro. This suggests that pathogenesis in Sjogren's syndrome may 
      involve a TNF-controlled cross-talk between apoptotic ductal and CCL20-attracted 
      dendritic cells via the CD137/CD137L signalling pathway.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Oral Biology, University of Missouri-Kansas City School of 
      Dentistry, 650 E 25th Street, Kansas City, MO 64108, United States.
FAU - Shnyra, Alexander
AU  - Shnyra A
FAU - Africa, Charlene
AU  - Africa C
FAU - Warholic, Christopher
AU  - Warholic C
FAU - McArthur, Carole
AU  - McArthur C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090828
PL  - England
TA  - Arch Oral Biol
JT  - Archives of oral biology
JID - 0116711
RN  - 0 (Autoantibodies)
RN  - 0 (CCL20 protein, human)
RN  - 0 (Chemokine CCL20)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFRSF9 protein, human)
RN  - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Apoptosis/*immunology
MH  - Autoantibodies/immunology
MH  - Autoimmune Diseases/*immunology
MH  - Cell Line
MH  - Chemokine CCL20/biosynthesis
MH  - Dendritic Cells/immunology
MH  - Gene Expression Profiling
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*immunology
MH  - Jurkat Cells
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptor Cross-Talk
MH  - Receptors, Tumor Necrosis Factor/*immunology
MH  - Salivary Glands/cytology/*immunology
MH  - Sialadenitis/*immunology
MH  - Signal Transduction
MH  - Sjogren's Syndrome/*immunology
MH  - TNF-Related Apoptosis-Inducing Ligand/immunology
MH  - Tumor Necrosis Factor Receptor Superfamily, Member 9/biosynthesis/immunology
MH  - Tumor Necrosis Factor-alpha/immunology
EDAT- 2009/09/01 06:00
MHDA- 2010/04/09 06:00
CRDT- 2009/09/01 09:00
PHST- 2009/03/03 00:00 [received]
PHST- 2009/07/27 00:00 [revised]
PHST- 2009/07/31 00:00 [accepted]
PHST- 2009/09/01 09:00 [entrez]
PHST- 2009/09/01 06:00 [pubmed]
PHST- 2010/04/09 06:00 [medline]
AID - S0003-9969(09)00202-7 [pii]
AID - 10.1016/j.archoralbio.2009.07.011 [doi]
PST - ppublish
SO  - Arch Oral Biol. 2009 Nov;54(11):986-96. doi: 10.1016/j.archoralbio.2009.07.011. 
      Epub 2009 Aug 28.