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Xu X.,China Agricultural University | Li H.,Shanxi Agricultural University | Hou X.,China Agricultural University | Li D.,China Agricultural University | And 7 more authors.
Mediators of Inflammation | Year: 2015

Reactive oxygen species (ROS) and oxidative stress are thought to play a central role in potentiating macrophage activation, causing excessive inflammation, tissue damage, and sepsis. Recently, we have shown that punicalagin (PUN) exhibits anti-inflammatory activity in LPS-stimulated macrophages. However, the potential antioxidant effects of PUN in macrophages remain unclear. Revealing these effects will help understand the mechanism underlying its ability to inhibit excessive macrophage activation. Hemeoxygenase-1 (HO-1) exhibits antioxidant activity in macrophages. Therefore, we hypothesized that HO-1 is a potential target of PUN and tried to reveal its antioxidant mechanism. Here, PUN treatment increased HO-1 expression together with its upstream mediator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). However, specific inhibition of Nrf2 by brusatol (a specific Nrf2 inhibitor) dramatically blocked PUN-induced HO-1 expression. Previous research has demonstrated that the PI3K/Akt pathway plays a critical role in modulating Nrf2/HO-1 protein expression as an upstream signaling molecule. Here, LY294002, a specific PI3K/Akt inhibitor, suppressed PUN-induced HO-1 expression and led to ROS accumulation in macrophages. Furthermore, PUN inhibited LPS-induced oxidative stress in macrophages by reducing ROS and NO generation and increasing superoxide dismutase (SOD) 1 mRNA expression. These findings provide new perspectives for novel therapeutic approaches using antioxidant medicines and compounds against oxidative stress and excessive inflammatory diseases including tissue damage, sepsis, and endotoxemic shock. © 2015 Xiaolong Xu et al. Source

Liu X.,China Agricultural University | Liu X.,Beijing Key Laboratory for Dairy Cow Nutrition | Shi Y.,China Agricultural University | Shi Y.,Beijing Key Laboratory for Dairy Cow Nutrition | And 11 more authors.
International Journal of Hyperthermia | Year: 2014

Purpose: This study aimed to investigate immune-related gene expression in rat small intestine after heat stress. Materials and methods: Twelve Sprague Dawley (SD) rats were randomly divided into control and heat-stressed groups. Rats in both groups were housed at 25°C with 60% relative humidity. The heat-stressed group was subjected to 40°C for 2h/day for 3 days. After heat stress, the mRNA expression profile of small intestine epithelial tissue was evaluated by microarray analysis. Results: A total of 23 genes related to immune responses were significantly altered, of which 12 genes were up-regulated and 11 genes were down-regulated. Conclusions: Microarray analysis demonstrated the JAK-STAT pathway had a potentially important role in the regulation of inflammation in the small intestine, and changes in antigen presentation might reduce intestinal immune responses after heat stress. © 2014 Informa UK Ltd. Source

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