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Blockage of heat shock protein receptor CD91 ameliorates coxsackievirus B3‐induced myocarditis
Author(s) -
CHEN YU,
Liu Youan,
Wang Jiafang,
Li Guohua,
Binder Robert J.,
Noble Earl G.,
Liu∗ Peter P.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a770-b
Subject(s) - heat shock protein , myocarditis , inflammation , antibody , hsp70 , coxsackievirus , viral myocarditis , myocyte , shock (circulatory) , receptor , medicine , immunology , chemistry , virus , enterovirus , biochemistry , gene
Heat shock proteins (Hsps) protect cell against deleterious stimuli, however, in vitro studies indicate that Hsps induce pro‐inflammatory cytokines and cell injury. We hypothesize that when cardiac myocytes are damaged and cell integrity is compromised, Hsps will be released into the circulation and trigger cardiac inflammation by interacting with heat shock protein receptor CD91. Mice were allocated randomly into the groups treated with PBS, anti‐CD91 IgG, control IgG, heat shock protein gp96, or gp96 + anti‐CD91 IgG respectively, and then subjected to the inoculation of Coxsackie virus B3 (CVB3). The treatment with anti‐CD91 antibody at different dosages significantly improved animal survival at day 14 in CVB3‐induced myocarditis (for 7.5 μg, 63.6%; for 15 μg, 64%; for 30 μg, 93.5%) vs PBS (30%) and control IgG (34%) treatments. Anti‐CD91 antibody also improved the lowest survival rate of animals treated with gp96 (64.6% vs 20% respectively, p<0.05). Anti‐CD91 treatment apparently ameliorated the viral myocarditis by suppressing cell infiltration and NF‐kB nuclear translocation. The plasma levels of Hsp47, Hsp70 and Hsp90 were increased after infection and the increased levels were suppressed by anti‐CD91 antibody. This study suggests that Hsps released from myocytes may trigger cardiac inflammation by activating CD91. The blockage of CD91 ameliorates CVB3‐induced myocarditis. Supported by Heart & Stroke Foundation of Canada.