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

Iwata, Daiju; Kitamura, Mizuki; Kitaichi, Nobuyoshi; Saito, Yoshinari; Kon, Shigeyuki; Namba, Kenichi; Morimoto, Junko; Ebihara, Akiko; Kitamei, Hirokuni; Yoshida, Kazuhiko; Ishida, Susumu; Ohno, Shigeaki; Uede, Toshimitsu; Onoé, Kazunori; Iwabuchi, Kazuya

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

Iwata, Daiju; Kitamura, Mizuki; Kitaichi, Nobuyoshi et al.

Experimental Eye Research, 2010, 90(1), 41-48

Permalink : https://hdl.handle.net/2115/42602

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アクセス権	open access
URI	https://hdl.handle.net/2115/42602
タイトル	Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA
著者	Iwata, Daiju ; Kitamura, Mizuki ; Kitaichi, Nobuyoshi ; Saito, Yoshinari ; Kon, Shigeyuki ; Namba, Kenichi ; Morimoto, Junko ; Ebihara, Akiko ; Kitamei, Hirokuni ; Yoshida, Kazuhiko ; Ishida, Susumu ; Ohno, Shigeaki ; Uede, Toshimitsu ; Onoé, Kazunori ; Iwabuchi, Kazuya
e-Rad_Researcher 70374402 著者名 Iwata, Daiju
著者名 Kitamura, Mizuki
e-Rad_Researcher 40431366 著者名 Kitaichi, Nobuyoshi
著者名 Saito, Yoshinari
著者名 Kon, Shigeyuki
e-Rad_Researcher 70333599 著者名 Namba, Kenichi
e-Rad_Researcher 50338208 著者名 Morimoto, Junko
著者名 Ebihara, Akiko
e-Rad_Researcher 90451426 著者名 Kitamei, Hirokuni
e-Rad_Researcher 90281807 著者名 Yoshida, Kazuhiko
e-Rad_Researcher 10245558 著者名 Ishida, Susumu
e-Rad_Researcher 50002382 著者名 Ohno, Shigeaki
e-Rad_Researcher 00160185 著者名 Uede, Toshimitsu
e-Rad_Researcher 40002117 著者名 Onoé, Kazunori
著者名 Iwabuchi, Kazuya
言語	英語
キーワード	inflammation
	EAU
	OPN
	RNA interference
	uveitis
発行日	2010-01
出版者	Elsevier Ltd.
収録物名	Experimental Eye Research
巻(号)	90(1)
ページ	41-48
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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0014-4835
関連情報	PMID 19766630
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.exer.2009.09.008