Matsumura R, Umemiya K, Goto T, Nakazawa T, Ochiai K, Kagami M, Tomioka H, Tanabe E, Sugiyama T, Sueishi M
Department of Internal Medicine, Toho University School of Medicine, Sakura Hospital, Japan.
Clin Exp Rheumatol. 2000 May-Jun;18(3):311-8.
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.
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.
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.
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.
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.
我们之前报道过，在干燥综合征（SS）所致严重涎腺炎患者中，Fas抗原在涎腺导管上皮细胞上强烈表达，且一些涎腺浸润细胞表达Fas配体。通过DNA缺口末端标记法在导管上皮细胞和一些浸润细胞中观察到凋亡变化。这些发现提示Fas - Fas配体系统可能在SS涎腺炎的发病机制中起作用。
为阐明与SS相关的涎腺炎中导管Fas抗原从头表达的机制，我们研究了细胞因子对人涎腺导管细胞系中Fas抗原的诱导作用及凋亡情况。
用人涎腺导管细胞系（HSG）与干扰素γ（IFN - γ）、肿瘤坏死因子α（TNF - α）、白细胞介素1β（IL - 1β）、白细胞介素2（IL - 2）、白细胞介素4（IL - 4）和粒细胞巨噬细胞集落刺激因子（GM - CSF）共同培养。通过免疫过氧化物酶细胞ELISA检测HSG中Fas抗原的表达。用DNA缺口末端标记法检测抗Fas抗体诱导凋亡过程中DNA链断裂的出现情况。
未受刺激的HSG细胞组成性表达低水平的Fas抗原。IFN - γ和TNF - α持续上调Fas的组成性水平。相比之下，IL - 1β、IL - 2、IL - 4和GM - CSF对Fas水平无影响。响应IFN - γ或TNF - α而表达Fas抗原的HSG细胞易被抗Fas抗体诱导凋亡。
我们的发现提示，浸润淋巴细胞分泌的IFN - γ或TNF - α诱导与SS相关的涎腺炎中导管Fas表达及导管凋亡。
