Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice.
Experimental autoimmune uveoretinitis (EAU) serves as a model of human endogeneous uveitis. In the present study we examined whether induction of heat shock protein (HSP) 70 by oral geranylgeranylacetone (GGA) administration had a therapeutic effect on murine EAU. When C57BL/6 mice that had received oral administration of GGA (500mg/kg) were immunized with interphotoreceptor retinoid-binding protein (IRBP)-derived peptide plus adjuvants, the expression levels of HSP70 mRNA and protein were rapidly and transiently upregulated in eyes of the GGA-treated mice, compared with those from vehicle-pretreated and IRBP-immunized mice. The antigen-specific T cell proliferation was partially suppressed in these mice treated with GGA. The mean EAU scores of the GGA-treated mice on day 21 and 28 (2.4+/-0.2 and 2.1+/-0.2, respectively) were significantly lower than those in the controls (3.0+/-0.1 and 2.6+/-0.2, respectively p<0.01). The histopathological severity of the GGA-treated mice (average 0.33) was markedly milder than that in the controls (average 1.63, p<0.05) at day 21. The present findings demonstrate that the pharmacological induction of HSP70 may be applicable to the amelioration of ocular autoimmune diseases.
Kitamei
Hirokuni
H
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. hiromekita@yahoo.co.jp <hiromekita@yahoo.co.jp>
Kitaichi
Nobuyoshi
N
Yoshida
Kazuhiko
K
Nakai
Akira
A
Fujimoto
Mitsuaki
M
Kitamura
Mizuki
M
Iwabuchi
Kazuya
K
Miyazaki
Akiko
A
Namba
Kenichi
K
Ohno
Shigeaki
S
Onoé
Kazunori
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000378:metabolism / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000627:therapeutic use*; D005123:Eye / Q000187:drug effects / Q000473:pathology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects; D014605:Uveitis / Q000378:metabolism / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; C031049:geranylgeranylacetone