Biomedical subjects

Yu Hirai

Publications and source records attributed to Yu Hirai.

4 recordsLinked to original sources

PubMed2006

The Kupffer cell protects against acute lung injury in a rat peritonitis model: role of IL-10.

The possibility that Kupffer cells (KCs) play key beneficial and deleterious roles in multiple organ injury in sepsis has been discussed. The role of KCs in lung injury in a rat peritonitis model was investigated. Specifically, the involvement of interleukin (IL)-10, which has anti-inflammatory effects, was examined. Rats were given saline or gadolinium chloride (GdCl3), a KC toxicant, 24 h before cecal ligation and puncture (CLP). Survival was assessed for 7 days after CLP. The liver, lung, and serum were harvested, and the expression of cytokines was assessed. Macrophages were isolated from each organ after CLP, and the mRNA expression of inflammatory mediators was assessed. GdCl3 treatment increased lung injury and mortality. Plasma endotoxin levels were significantly greater, whereas serum IL-10 levels were lower in the GdCl3 than in the control group after CLP. IL-10 levels were significantly greater in the aorta than the hepatic vein. The mRNA expression of IL-10 was less in KCs from the GdCl3 than the control group. In the liver, the expression of IL-10 increased rapidly and continuously, up to 9 h in the control group, but values were significantly lower in the GdCl3 group. Rabbit anti-rat IL-10 antibodies were injected just after CLP to investigate the effects of immunoneutralization of endogenously produced IL-10. In the antibody-treated group, lung injury and mortality increased compared with animals treated with rabbit immunoglobulin G. Taken together, these results indicate that KCs play a protective role in lung injury in sepsis by production of IL-10.

Acute Disease↗

PubMed2005

Role of Kupffer cells in lung injury in rats administered endotoxin 1.

The purpose of this study was to investigate the regulation of lung macrophages (Muvarphis) by Kupffer cells (KCs) in lung injury caused by endotoxemia. Phenotypic differences in tissue Muvarphis were also investigated. Muvarphis were isolated from gadolinium chloride (GdCl(3))- or saline-treated rats 2 h after saline or lipopolysaccharide (LPS) administration. Furthermore, rats were given GdCl(3) 24 h prior to LPS administration, and survival rate was assessed for 24 h. Moreover, lung edema was assessed 9 h after LPS injection. Expression of inflammatory mediators was measured in the liver and lung. KCs were divided into three subpopulations based on size and phagocytosis. The expression of TNF-alpha and MIP-2 was greater in the small KCs and lung Muvarphis, while the expression of IL-6, IL-10, and MCP-1 was greater in the large and intermediate KCs. GdCl(3) eliminated ED2-positive large KCs and did not have any effect on the lung Muvarphis. The number of ED1-positive KCs increased significantly in both organs after LPS challenge and was reduced by GdCl(3). The population of ED2-positive KCs did not change following LPS administration. GdCl(3) completely prevented increases in lung microvascular permeability and mortality after LPS infusion. After LPS administration, expression of TNF-alpha and IL-6 increased rapidly and then decreased gradually in both organs. GdCl(3) inhibited these increases in the liver significantly and enhanced the expression of MCP-1 and IL-10 in the lung 9 h after LPS administration. Thus, the heterogeneous response of KCs to endotoxin leads to production of certain cytokines and chemokines that affect lung function.

Animals↗

PubMed2004

Phosphorylated alpha-synuclein in normal mouse brain.

alpha-Synuclein phosphorylated at Ser129 is the main component of Lewy bodies of Parkinson's and closely related diseases. We studied, by quantitative immunoblotting, changes in the phosphorylation level of alpha-synuclein in the mouse brains subjected to cold water stress. Relative basal level of alpha-synuclein phosphorylation at Ser129 was 40% higher in the striatum compared with the hippocampus. The phosphorylation level decreased to 57% in the striatum 20 min after 5 min of cold water stress, and also in the hippocampus and cortex to lesser degrees. Recovery to basal levels took place over several hours. The stress-induced temporary dephosphorylation was of smaller magnitude in the striatum of aged (18 months) mice. These results show that alpha-synuclein phosphorylation level at Ser129 in vivo responds to physiological stimuli. Relative prominence and age sensitivity of this phenomenon in the striatum may be relevant to the pathogenesis of Parkinson's disease.

Aging↗

PubMed2004

Medium-chain triglycerides enhance secretory IgA expression in rat intestine after administration of endotoxin.

The purpose of this study was to determine whether medium-chain triglycerides (MCTs) modulate the inflammatory immune response to LPS and enhance the expression of secretory IgA in the rat intestine. Rats were given either corn oil or MCTs by gavage daily for 1 wk, and LPS or saline vehicle was administered via the tail vein. They were then killed, and serum and sections from the gut were collected for further analysis. Western blot analysis for secretory IgA revealed that MCTs significantly enhanced its expression in the ileum compared with corn oil in rats administered saline. After LPS challenge, expression of secretory IgA was decreased in the corn oil group but not in the MCTs group. The mRNA expression of IL-6 was assessed by real-time RT-PCR, because IL-6 regulates secretory IgA in the intestine. The expression was significantly greater in the MCTs group than in the corn oil group after LPS injection. Increases in expression of proinflammatory cytokines or chemokines such as TNF-alpha, IL-18, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 in the ileum were significantly blunted by MCTs. In addition, the mRNA expression of the Th2 IgA-stimulating cytokine IL-10 in the ileum and Peyer's patches was significantly greater in the MCTs than the corn oil group. In contrast, the mRNA expression of the Th1 IgA-inhibiting cytokine interferon-gamma was blunted by MCTs. As a result, intestinal injury was significantly reduced. Therefore, MCTs protect the gut by modulating the immune response to LPS and enhancing secretory IgA expression.

Animals↗