Nakamura Hideki
Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences.
Nihon Rinsho Meneki Gakkai Kaishi. 2014;37(3):117-24. doi: 10.2177/jsci.37.117.
Chronic sialadenitis in Sjögren's syndrome (SS) is associated with cell death induced by Fas or cytotoxic granules. Furthermore, tumor necrosis factor-related apoptosis inducing ligand or toll-like receptor3 are known to induce apoptosis in the salivary gland epithelial cells (SGECs) derived from patients with SS. Anti-apoptotic molecules that are closely related to epidermal growth factor are known to inhibit apoptosis. Epidemiologically, high prevalence of HTLV-I in primary Sjögren's syndrome (SS) patients has been found in an endemic area. However, by comparison of radiographic imaging with mononuclear cells (MNCs) infiltration of LSGs, we have found that there are significantly fewer abnormalities determined by sialography in HTLV-I-seropositive SS patients in comparison with HTLV-I-seronegative SS patients irrespective of similar grade of MNCs infiltration. In HTLV-I-seropositive SS patients, low frequency of salivary gland destruction was observed and this phenomenon was associated with frequency of the ectopic germinal center (GC). Then, we show cytokine profile in culture supernatant of salivary gland epithelial cells co-cultured with HCT-5 established from spinal fluid of patients with HAM. Up-regulation of adhesion molecule or migration factor was observed in culture supernatant. On the other hand, co-cultured cell lysate showed apoptotic and anti-apoptotic molecules without increase of apoptosis. Detailed molecular mechanisms in these processes are under study.
干燥综合征(SS)中的慢性涎腺炎与Fas或细胞毒性颗粒诱导的细胞死亡有关。此外,已知肿瘤坏死因子相关凋亡诱导配体或Toll样受体3可诱导SS患者来源的涎腺上皮细胞(SGECs)凋亡。已知与表皮生长因子密切相关的抗凋亡分子可抑制凋亡。在流行病学上,在一个流行地区发现原发性干燥综合征(SS)患者中HTLV-I的高患病率。然而,通过对颌下腺(LSGs)的放射影像学与单核细胞(MNCs)浸润进行比较,我们发现,无论MNCs浸润程度相似,HTLV-I血清阳性的SS患者通过涎管造影确定的异常明显少于HTLV-I血清阴性的SS患者。在HTLV-I血清阳性的SS患者中,观察到涎腺破坏的频率较低,并且这种现象与异位生发中心(GC)的频率有关。然后,我们展示了与从HAM患者脑脊液中建立的HCT-5共同培养的涎腺上皮细胞培养上清液中的细胞因子谱。在培养上清液中观察到黏附分子或迁移因子的上调。另一方面,共同培养的细胞裂解物显示出凋亡和抗凋亡分子,但凋亡没有增加。这些过程中的详细分子机制正在研究中。