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Okamoto, S. et al.

Macrophage inflammatory protein-1alpha plays a crucial role in concanavalin A-induced liver injury through induction of proinflammatory cytokines in mice.

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-1alpha (MIP-1alpha), 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-1alpha antibody, recombinant murine-MIP-1alpha and gadolinium chloride (GdCl(3)) were administrated prior to Con A injection. Plasma alanine aminotransferase ( ALT), MIP-1alpha, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) levels were determined and histological assessment of the liver was performed. RESULTS:: Plasma MIP-1alpha 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-1alpha antibody pretreatment. The elevated plasma ALT level after Con A injection was further enhanced by recombinant murine-MIP-1alpha. The elevated plasma TNF-alpha and IFN-gamma levels after Con A injection were inhibited by anti-MIP-1alpha antibody, and enhanced by recombinant murine-MIP-1alpha. GdCl(3) pretreatment inhibited the elevated plasma MIP-1alpha and ALT levels. CONCLUSIONS:: These findings suggest that MIP-1alpha 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.[1]

References

Macrophage inflammatory protein-1alpha plays a crucial role in concanavalin A-induced liver injury through induction of proinflammatory cytokines in mice. Okamoto, S., Yokohama, S., Yoneda, M., Haneda, M., Nakamura, K. Hepatol. Res. (2005) [Pubmed]

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