Abstract

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Background: Theanine, which is hydrolyzed into glutamic acid (Glu), excerts beneficial effects on organ metabolism. However, there is little scientific evidence that Glu influences inflammatory mediator such as tumor necrosis factor (TNF)-a and nitric oxide (NO).In inflamed liver, proinflammatory cytokines stimulate liver cells, followed by the induction of inducible NO synthase (iNOS). Excessive NO produced by iNOS has been implicated as one of the factors in liver injury. Thus it is essential to inhibit iNOS induction for the prevention of liver injury. In this study, we examined interleukin (IL)-1β-stimulated hepatocytes as a simple "in vitro injury model" to investigate liver protective effecs of Glu.
Methods: Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of Glu. Inflammatory biomarkers including iNOS and TNF-a were analyzed.
Results: Simultaneous addition of IL-1β and Glu decreased the expression levels of iNOS protein and its mRNA, resulting in the inhibition of NO production. Glu also reduced RNA expressions of TNF-a and IL-6. Glu inhibited two essential signaling pathways for iNOS induction, IKB/NF-KB activation and type I IL-1 receptor upregulation. Transfection experiments revealed that Glu reduced the levels of iNOSmRNA at the promoter activation and mRNA stabilization steps. Delayed administration of Glu after IL-1β addition also inhibited iN induction.
Conclusions: Glu influenced the induction of pro-inflammatory mediators, such as iNOS and TNF-α, in part through the inhib including liver.

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