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

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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
RNA interference
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)
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)

Submitter: 岩渕 和也

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