Cell death of salivary gland epithelial cells and involvement of HTLV-I in Sjögren's syndrome

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  • NAKAMURA Hideki
    Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences

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  • シェーグレン症候群唾液腺細胞死とHTLV-Iの関与

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Abstract

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.

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