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Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

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タイトル: Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA
著者: Iwata, Daiju 著作を一覧する
Kitamura, Mizuki 著作を一覧する
Kitaichi, Nobuyoshi 著作を一覧する
Saito, Yoshinari 著作を一覧する
Kon, Shigeyuki 著作を一覧する
Namba, Kenichi 著作を一覧する
Morimoto, Junko 著作を一覧する
Ebihara, Akiko 著作を一覧する
Kitamei, Hirokuni 著作を一覧する
Yoshida, Kazuhiko 著作を一覧する
Ishida, Susumu 著作を一覧する
Ohno, Shigeaki 著作を一覧する
Uede, Toshimitsu 著作を一覧する
Onoé, Kazunori 著作を一覧する
Iwabuchi, Kazuya 著作を一覧する
キーワード: inflammation
RNA interference
発行日: 2010年 1月
出版者: Elsevier Ltd.
誌名: Experimental Eye Research
巻: 90
号: 1
開始ページ: 41
終了ページ: 48
出版社 DOI: 10.1016/j.exer.2009.09.008
抄録: Osteopontin (OPN) is elevated during the progression of experimental autoimmune uveoretinitis (EAU) in C57BL/6 (B6) mice. Furthermore, EAU symptoms are ameliorated in OPN knockout mice or in B6 mice treated with anti-OPN antibody (M5). Recently, OPN has been shown to promote the Th1 response not only in the extracellular space as a secretory protein but also in cytosol as a signaling component. Thus, we attempted to reduce OPN in both compartments by using a small interfering RNA (siRNA) targeting the OPN coding sequence (OPN-siRNA). EAU was induced in B6 mice by immunization with human interphotoreceptor retinoid-binding protein (hIRBP) peptide sequence 1-20. The OPN- or control-siRNA was administered with hydrodynamic methods 24 hours before and simultaneously with immunization (prevention regimen). When plasma OPN levels were quantified following siRNA administration with the prevention regimen, the level in the OPN-siRNA-treated group was significantly lower than that in the control-siRNA-treated group. Accordingly, the clinical and histopathological scores of EAU were significantly reduced in B6 mice when siRNA caused OPN blockade. Furthermore, TNF-α, IFN-γ, IL-2, GM-CSF and IL-17 levels in the culture supernatants were markedly suppressed in the OPN-siRNA-treated group, whereas the proliferative responses of T lymphocytes from regional lymph nodes against immunogenic peptides was not significantly reduced. On the other hand, the protection was not significant if the mice received the OPN-siRNA treatment on day 7 and day 8 after immunization when the clinical symptoms appeared overt (reversal regimen). Our results suggest that OPN blockade with OPN-siRNA can be an alternative choice for the usage of anti-OPN antibody and controlling uveoretinitis in the preventive regimen.
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 岩渕 和也


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