| Title: | Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA |
| Authors: | Iwata, Daiju Browse this author →KAKEN DB |
| Kitamura, Mizuki Browse this author |
| Kitaichi, Nobuyoshi Browse this author →KAKEN DB |
| Saito, Yoshinari Browse this author |
| Kon, Shigeyuki Browse this author |
| Namba, Kenichi Browse this author →KAKEN DB |
| Morimoto, Junko Browse this author →KAKEN DB |
| Ebihara, Akiko Browse this author |
| Kitamei, Hirokuni Browse this author →KAKEN DB |
| Yoshida, Kazuhiko Browse this author →KAKEN DB |
| Ishida, Susumu Browse this author →KAKEN DB |
| Ohno, Shigeaki Browse this author →KAKEN DB |
| Uede, Toshimitsu Browse this author →KAKEN DB |
| Onoé, Kazunori Browse this author →KAKEN DB |
| Iwabuchi, Kazuya Browse this author |
| Keywords: | inflammation |
| EAU |
| OPN |
| RNA interference |
| uveitis |
| Issue Date: | Jan-2010 |
| Publisher: | Elsevier Ltd. |
| Journal Title: | Experimental Eye Research |
| Volume: | 90 |
| Issue: | 1 |
| Start Page: | 41 |
| End Page: | 48 |
| Publisher DOI: | 10.1016/j.exer.2009.09.008 |
| PMID: | 19766630 |
| Abstract: | 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/42602 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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