Journal
BIOTECHNOLOGY LETTERS
Volume 34, Issue 12, Pages 2175-2182Publisher
SPRINGER
DOI: 10.1007/s10529-012-1022-4
Keywords
Cytokine; Endotoxemia; High mobility group box 1; Liver injury; Transcription factor activator protein-1; Tumor necrosis factor-alpha
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Funding
- Grants-in-Aid for Scientific Research [22590958] Funding Source: KAKEN
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The effect of T-5224, a selective inhibitor of c-Fos/activator protein (AP)-1, on lipopolysaccharide (LPS) induced liver injury was examined in mice. Administration of LPS (10 mg kg(-1), i.p.) markedly increased serum levels of tumor necrosis factor-alpha (TNF alpha), high mobility group box 1 (HMGB1), alanine aminotransferase/aspartate aminotransferase (ALT/AST), liver tissue levels of macrophage-inflammatory protein-1 alpha (MIP-1 alpha) and monocyte chemoattractant protein-1 (MCP-1), as well as hepatic necrosis and inflammation, leading to 67 % lethality. Administration of T-5224 (300 mg kg(-1), p.o.) after intraperitoneal injection of LPS imparted appreciable protection against acute elevations in serum levels of TNF alpha, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1 alpha and MCP-1, and reduced the lethality (27 %). These data indicate that T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice.
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