Role of metallothionein in coagulatory disturbance and systemic inflammation induced by lipopolysaccharide in mice

• Published in: The FASEB journal 2006-03, Vol.20 (3), p.533-535
• Main Authors: Inoue, Ken-ichiro, Takano, Hirohisa, Shimada, Akinori, Wada, Emiko, Yanagisawa, Rie, Sakurai, Miho, Satoh, Masahiko, Yoshikawa, Toshikazu
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Chemokine CCL3; Chemokine CCL4; Chemokine CXCL2; Chemotactic Factors - biosynthesis; Chemotactic Factors - genetics; cytokine; Cytokines - biosynthesis; Cytokines - genetics; endothelial damage; Gene Expression Regulation - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Homeostasis - physiology; Inflammation - chemically induced; Inflammation - physiopathology; Interleukin-1 - biosynthesis; Interleukin-1 - genetics; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Kidney - metabolism; Kidney - pathology; Lipopolysaccharides - pharmacology; Lipopolysaccharides - toxicity; Liver - metabolism; Liver - pathology; Lung - metabolism; Lung - pathology; Macrophage Inflammatory Proteins - biosynthesis; Macrophage Inflammatory Proteins - genetics; Metallothionein - deficiency; Metallothionein - genetics; Metallothionein - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Monokines - biosynthesis; Monokines - genetics; Multiple Organ Failure - chemically induced; Multiple Organ Failure - physiopathology; Neutrophils - pathology; systemic inflammatory response syndrome; Systemic Inflammatory Response Syndrome - chemically induced; Systemic Inflammatory Response Syndrome - physiopathology; Thrombophilia - chemically induced; Thrombophilia - physiopathology
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.05-3864fje

Although metallothionein (MT) can be induced by inflammatory mediators, its roles in coagulatory disturbance during inflammation are poorly defined. We determined whether MT protects against coagulatory and fibrinolytic disturbance and systemic inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) in MT‐I/II null (?/?) and wild‐type (WT) mice. As compared with WT mice, MT (?/?) mice revealed significant prolongation of prothrombin and activated partial thromboplastin time, a significant increase in the levels of fibrinogen and fibrinogen/fibrin degradation products, and a significant decrease in activated protein C, after LPS treatment. LPS induced inflammatory organ damages in the lung, kidney, and liver in both genotypes of mice. The damages, including neutrophil infiltration, were more prominent in MT (?/?) mice than in WT mice after LPS treatment. In both genotypes of mice, LPS enhanced protein expression of interleukin (IL)‐1?, IL‐6, granulocyte/macrophage‐colony‐stimulating factor, macrophage inflammatory protein (MIP)‐1?, MIP‐2, macrophage chemoattractant protein‐1, and keratinocyte chemoattractant in the lung, kidney, and liver and circulatory levels of IL‐1?, IL‐6, MIP‐2, and KC. In overall trends, however, the levels of these proinflammatory proteins were greater in MT (?/?) mice than in WT mice after LPS challenge. Our results suggest that MT protects against coagulatory and fibrinolytic disturbance and multiple organ damages induced by LPS, at least partly, via the inhibition of the expression of proinflammatory proteins.