Regulation of apoptotic cell death by cytokines in a human salivary gland cell line: distinct and synergistic mechanisms in apoptosis induced by tumor necrosis factor alpha and interferon gamma.

Abstract

We examined the mechanisms of apoptosis in a human salivary gland (HSG) cell line induced by tumor necrosis factor (TNF) alpha and interferon (IFN) gamma. DNA fragmentation and the activation of caspase-3 were determined in HSG cells cultured with TNF-alpha or IFN-gamma. Mitochondrial dysfunction also appeared to be involved in the process because a disruption of mitochondrial transmembrane potential with the activation of caspase-9 was demonstrated in TNF-alpha- and IFN-gamma-stimulated HSG cells. Activation of caspase-8 was thought to be essential in TNF-alpha--induced apoptosis of HSG cells; however, the activation of caspase-8 was not involved in IFN-gamma-induced apoptosis of HSG cells. In contrast, Bcl-2 appeared to be an indispensable regulatory molecule in IFN-gamma-induced, but not in TNF-alpha-induced, apoptosis of HSG cells because its expression was inhibited in IFN-gamma-stimulated, but not in TNF-alpha-stimulated, cells. The inhibitory effect of IFN-gamma in Bcl-2 expression was enhanced by coadministration of TNF-alpha and, interestingly, apoptosis of HSG cells, as assessed by DNA fragmentation and the activation of caspase-9 and caspase-3, and disruption of mitochondrial transmembrane potential was also synergistically augmented by TNF-alpha and IFN-gamma. Our results suggest that cytokines expressed in the salivary glands of patients with Sjögren syndrome play an important role in regulating apoptosis of acinar-ductal epithelial cells through distinct and synergistic mechanisms, thereby modulating salivary gland function in patients with Sjögren syndrome.

• Authors: Makoto Kamachi, Atsushi Kawakami, Satoshi Yamasaki, Ayumi Hida, Tomoki Nakashima, Hideki Nakamura, Hiroaki Ida, Masako Furuyama, Koto Nakashima, Kazutaka Shibatomi, Taiichiro Miyashita, Kiyoshi Migita, Katsumi Eguchi
• Journal: The Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 139 Issue 1 Pg. 13-9 (Jan 2002) ISSN: 0022-2143 [Print] United States
• PMID: 11873240 (Publication Type: Journal Article)

Chemical References

• Enzyme Precursors
• Proto-Oncogene Proteins c-bcl-2
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• CASP3 protein, human
• CASP8 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases
• Cell Line
• Drug Synergism
• Enzyme Activation (drug effects)
• Enzyme Precursors
• Humans
• Interferon-gamma (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• Salivary Glands (cytology, drug effects)
• Tumor Necrosis Factor-alpha (pharmacology)