当前位置： SCI文献检索 > EXPERIMENTAL EYE RESEARCH期刊下所有文献 > Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA.

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

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 h 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-alpha, IFN-gamma, 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.

journal_name

Exp Eye Res

journal_title

Experimental eye research

authors

Iwata D,Kitamura M,Kitaichi N,Saito Y,Kon S,Namba K,Morimoto J,Ebihara A,Kitamei H,Yoshida K,Ishida S,Ohno S,Uede T,Onoé K,Iwabuchi K

doi

10.1016/j.exer.2009.09.008

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

41-8

issue

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(09)00276-0

journal_volume

pub_type

杂志文章

在线工具

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