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Thioredoxin May Exert a Protective Effect Against Tissue Damage Caused by Oxidative Stress in Salivary Glands of Patients with Sjögren's Syndrome CHIYO KURIMOTO, SEIJI KAWANO, GOH TSUJI, SAORI HATACHI, TAKUMI JIKIMOTO, DAISUKE SUGIYAMA, SHIMPEI KASAGI, TAKAHIDE KOMORI, HAJIME NAKAMURA, JUNJI YODOI, and SHUNICHI KUMAGAI
ABSTRACT. Methods. Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2¢-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-g (IFN-g) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-g and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining. Results. Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-g-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX. Conclusion. Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage. (First Release Sept 15 2007; J Rheumatol 2007;34:2035-43) Key Indexing Terms:
SJÖGREN'S SYNDROME
From the Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Japan. Supported in part by a Grant-in-Aid for Scientific Research (no. 14370164) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. C. Kurimoto, MD; S. Kawano, MD, PhD; G. Tsuji, MD, PhD Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine; S. Hatachi, MD, PhD, Department of Clinical Immunology and Rheumatology, Kitano Hospital, Osaka; T. Jikimoto, MT; D. Sugiyama, MD; S. Kasagi, MD, Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine; T. Komori, MD, PhD, Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine; H. Nakamura, MD, PhD, Department of Experimental Therapeutics, Translational Research Center, Kyoto University, Kyoto; J. Yodoi, MD, PhD, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto; S. Kumagai, MD, PhD, Professor, Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine. Address reprint requests to Prof. S. Kumagai, Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. E-mail: kumagais@kobe-u.ac.jp. Accepted for publication July 5, 2007. |
