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M Kagami

Publications and source records attributed to M Kagami.

62 records · Page 4Linked to original sources
PubMedDate not supplied

Interferon gamma and tumor necrosis factor alpha induce Fas expression and anti-Fas mediated apoptosis in a salivary ductal cell line.

BACKGROUND: We previously reported that Fas antigen was strongly expressed on salivary duct epithelial cells and that some salivary infiltrating cells showed the Fas ligand in patients with severe sialoadenitis due to Sjögren's syndrome (SS). Apoptotic changes were observed in ductal epithelial cells and some infiltrating cells by DNA nick end labeling methods. These findings suggest that the Fas-Fas ligand system may play a role in the pathogenesis of sialoadenitis in SS. OBJECTIVE: To elucidate the mechanism of the de novo expression of ductal Fas antigen in sialoadenitis associated with SS, we investigated the induction of Fas antigen and apoptosis by cytokines in a human salivary duct cell line. METHODS: Human salivary duct cell line (HSG) was cultured with interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin 4 (IL-4), and granulocyte monocyte colony stimulating factor (GM-CSF). The expression of Fas antigen in HSG was examined by immunoperoxidase cell ELISA. The appearance of DNA strand breaks during apoptosis induced by anti-Fas antibody was detected by DNA nick end labeling methods. RESULTS: Unstimulated HSG cells constitutively expressed low levels of Fas antigen. IFN-gamma and TNF-alpha consistently upregulated constitutive levels of Fas. In contrast, IL-1 beta, IL-2, IL-4, and GM-CSF had no effect on Fas levels. HSG cells expressing Fas antigen in response to IFN-gamma or TNF-alpha were susceptible to apoptosis by anti-Fas antibody. CONCLUSION: Our findings suggest that IFN-gamma or TNF-alpha secreted by infiltrating lymphocytes induces ductal Fas expression and ductal apoptosis in sialoadenitis associated with SS.

Antineoplastic Agents↗
PubMedDate not supplied

Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells and of TRAIL receptors on salivary glands in patients with Sjögren's syndrome.

BACKGROUND: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal non-transformed tissues is unknown. OBJECTIVE: To evaluate the role of apoptosis mediated by TRAIL and TRAIL-receptor (TRAIL-R) system in lymphocytic sialadenitis in patients with Sjögren's syndrome. METHODS: The expression of TRAIL and TRAIL-R1, 2, 3 and 4 in lymphocytic sialadenitis was examined by immunoperoxidase staining in patients with Sjögren's syndrome and in normal subjects. To elucidate the mechanism of de novo expression of TRAIL-R1 antigen, we quantitatively investigated its induction by cytokines in human salivary duct cell line (HSG) by cell enzyme-linked immunosorbent assay. In human salivary duct cells stimulated by cytokines, we investigated the induction of apoptotic cell death by recombinant TRAIL protein. RESULTS: In patients with massive mononuclear cell infiltration, some infiltrating cells showed TRAIL. In patients with severe lymphocytic sialadenitis, TRAIL-R1, TRAIL-R2, or both were strongly expressed on the ductal epithelial cells. Neither TRAIL-R3 nor R4 were observed on ductal epithelium. In contrast, TRAIL-R1 and R2 were not found in the minor salivary glands of normal subjects or patients with mild lymphocytic sialadenitis. Unstimulated HSG cells did not express TRAIL-R1. Interferon-gamma (IFN-gamma) consistently upregulated levels of TRAIL-R1. In contrast, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), IL-2, and IL-4 had no effect on TRAIL-R1 levels. HSG cells expressing TRAIL-R1 in response to IFN-gamma were susceptible to apoptosis by recombinant TRAIL protein. CONCLUSION: Our findings suggest that TRAIL and TRAIL-R system may play a role in the pathogenesis of lymphocytic sialadenitis in patients with Sjögren's syndrome.

Adult↗
PubMedDate not supplied

Expression of ductal Fas antigen in sialoadenitis of Sjögren's syndrome.

OBJECTIVE: The expression of Fas antigen on ductal epithelial cells of sialoadenitis was examined in patients with Sjögren's syndrome (SS) and in normal subjects. METHODS: Minor salivary glands from the SS patients were examined by an immunohistochemical method using a new monoclonal antibody to the Fas antigen. RESULTS: In two patients with severe sialoadenitis, Fas was strongly expressed on the ductal epithelial cells. By contrast, the Fas antigen was not seen in the minor salivary glands of normal subjects nor in those with mild sialoadenitis. CONCLUSION: This finding suggests that the Fas antigen may play a role in the pathogenesis of sialoadenitis in SS by providing a specific target for cytotoxic T cells expressing the Fas ligand.

Adolescent↗
PubMedDate not supplied

Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients with Sjögren's syndrome.

OBJECTIVE: To evaluate the role of Fas-Fas ligand system-mediated apoptosis in the sialoadenitis and interstitial nephritis of Sjögren's syndrome. METHODS: The expression of Fas antigen and Fas ligand in sialoadenitis and interstitial nephritis was examined by immunoperoxidase staining and the reverse transcriptase-polymerase reaction (RT-PCR) in patients with Sjögren's syndrome and in normal subjects. The appearance of DNA strand breaks during apoptosis was detected in the tissue by DNA nick end labeling methods. RESULTS: In patients with severe sialoadenitis, Fas antigen was strongly expressed on the ductal epithelial cells. In contrast, Fas antigen was not seen in the minor salivary glands of normal subjects nor in patients with mild sialoadenitis. In patients with massive mononuclear cell infiltration, some of the infiltrating cells showed the Fas ligand. In patients with interstitial nephritis associated with Sjögren's syndrome, Fas was expressed on the tubular epithelial cells, while such expression was not observed in control subjects without interstitial nephritis. In the patients with interstitial nephritis, some of the infiltrating cells showed the Fas ligand. Apoptotic changes were observed in the ductal epithelial cells, tubular epithelial cells and some infiltrating cells by DNA nick end labeling methods. mRNA for the Fas antigen and Fas ligand was found to be expressed in the labial salivary glands from all SS patients by RT-PCR. CONCLUSION: The findings of this study suggest that the Fas-Fas ligand system may play a role in the pathogenesis of the sialoadenitis and interstitial nephritis of Sjögren's syndrome.

Adolescent↗