Interferon-gamma sensitizes the human salivary gland cell line, HSG, to tumor necrosis factor-alpha induced activation of dual apoptotic pathways

Activated immune cells secrete proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma) and Fas ligand (FasL) and these cytokines have been reported to induce apoptosis in numerous cell types. Apoptotic cell death has been associated with the progressio...

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Bibliographic Details
Published in:Apoptosis (London) 2006-12, Vol.11 (12), p.2205-2215, Article 2205
Main Authors: Kulkarni, Kashmira, Selesniemi, Kaisa, Brown, Thomas L
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Autoimmune diseases
BH3 Interacting Domain Death Agonist Protein - metabolism
Caspase 3 - metabolism
Caspase 9 - metabolism
Caspase-8
Caspase-9
Cell death
Cell Line
Cleavage
Cytokines
Dose-Response Relationship, Drug
Down-Regulation - drug effects
Enzyme Activation - drug effects
Exocrine glands
FasL protein
Humans
Immune system
Inflammation
Interferon
Interferon-gamma - pharmacology
Mitochondria
Models, Biological
Mortality
Necrosis
Poly(ADP-ribose) Polymerases - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Salivary gland
Salivary glands
Salivary Glands - cytology
Salivary Glands - drug effects
Sjogren's syndrome
Spectrin
Spectrin - metabolism
Substrates
Time Factors
Tumor Necrosis Factor-alpha - pharmacology
Tumor necrosis factor-TNF
Tumor necrosis factor-α
X-Linked Inhibitor of Apoptosis Protein - metabolism
γ-Interferon
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Summary:Activated immune cells secrete proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma) and Fas ligand (FasL) and these cytokines have been reported to induce apoptosis in numerous cell types. Apoptotic cell death has been associated with the progression of numerous autoimmune diseases. Proinflammatory cytokines are reportedly involved in apoptosis in the salivary glands of patients with Sjögren's syndrome (SS); an autoimmune disorder characterized by the destruction of salivary and lachrymal glands. In this study, we used the HSG cell line to determine if exposure to proinflammatory cytokines induces apoptosis in human salivary gland cells. In addition, we identified the mediators controlling the apoptotic process in response to TNF alpha and IFN gamma. TNF-alpha and IFN-gamma induced apoptosis in HSG cells and resulted in the activation of caspase 8 and the "death receptor" pathway. We further determined that caspase 9 and the "mitochondrial" pathway was also activated. Induction of the intrinsic and extrinsic pathways in HSG cells resulted in substrate cleavage by effector caspases, in particular the cleavage of alpha II spectrin, an autoantigen in Sjögren's syndrome. Our results suggest that HSG cells provide a model system to study processes regulating proinflammatory cytokine-induced apoptotic cell death.
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-006-0281-8