Macrophage inflammatory protein-1alpha plays a crucial role in concanavalin A-induced liver injury through induction of proinflammatory cytokines in mice.
著者
岡本, 聡
(Okamoto, Satoshi)
Yokohama, S
Yoneda, M
Haneda, M
Nakamura, K
上位タイトル
HEPATOLOGY RESEARCH
Vol.32,
No.1
(2005.
5)
,p.38-
45
Background/aims:The chemokines play roles in the development of immune mediated liver diseases. In this study, we investigate the involvement of macrophage inflammatory protein-1α (MIP-1α), one of the CC chemokines in concanavalin A (Con A)-induced liver injury in mice. Methods:Liver injury was induced by intravenous injection of Con A. Anti-mouse MIP-1α antibody, recombinant murine-MIP-1α and gadolinium chloride (GdCl_3) were administrated prior to Con A injection. Plasma alanine aminotransferase (ALT), MIP-1α, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) levels were determined and histological assessment of the liver was performed. Results:Plasma MIP-1α level was elevated after Con A injection. The elevated plasma ALT level, mortality rate and histological change after Con A injection were inhibited by anti-MIP-1α antibody pretreatment. The elevated plasma ALT level after Con A injection was further enhanced by recombinant murine-MIP-1α. The elevated plasma TNF-α and IFN-γ levels after Con A injection were inhibited by anti-MIP-1α antibody, and enhanced by recombinant murine-MIP-1α. GdCl_3 pretreatment inhibited the elevated plasma MIP-1α and ALT levels. Conclusions:These findings suggest that MIP-1α is produced from Kupffer cells after Con A injection, and this CC chemokine plays a crucial role in Con A-induced liver injury through induction of proinflammatory cytokines.
