Compared with LPS alone, the ethanol induction group produced significantly more TNF-α, nuclear NF-κB p65 and less cytoplasm IκB-α under LPS stimuli. CMZ abolished the effects of ethanol on LPS-stimulated NF-κB translocation

and TNF-α generation in Kupffer cells. In cultured Kupffer cell, using CMZ as inhibitor, ethanol-induced CYP2E1 overexpression was proved to contribute to the sensitization of Kupffer cells to LPS stimuli, with amplification of ROS production and activation of NF-κB, resulting in increased TNF-α production. “
“Human hepatocellular carcinoma (HCC) is an inflammation-induced cancer, which is the third-leading cause of cancer mortality worldwide. We investigated selleck chemicals Selleckchem GSK126 the role of the chemokine receptors, CCR5 and CCR1, in regulating inflammation and tumorigenesis in an inflammation-induced HCC model in mice. Multidrug resistance 2 gene (Mdr2)-knockout (Mdr2-KO) mice spontaneously develop chronic cholestatic hepatitis and fibrosis that is eventually followed by HCC. We generated two new strains from the Mdr2-KO mouse, the Mdr2:CCR5 and the Mdr2:CCR1 double

knockouts (DKOs), and set out to compare inflammation and tumorigenesis among these strains. We found that in Mdr2-KO mice lacking the chemokine receptor, CCR5 (Mdr2:CCR5 DKO mice), but not CCR1 (Mdr2:CCR1 DKO), macrophage recruitment and trafficking to the liver was http://www.selleck.co.jp/products/pci-32765.html significantly reduced. Furthermore, in the absence of CCR5, reduced inflammation was also associated with reduced periductal accumulation of CD24+ oval cells and abrogation of fibrosis. DKO mice for Mdr2 and CCR5 exhibited a significant

decrease in tumor incidence and size. Conclusions: Our results indicate that CCR5 has a critical role in both the development and progression of liver cancer. Therefore, we propose that a CCR5 antagonist can serve for HCC cancer prevention and treatment. (Hepatology 2013;53:1021–1030) In 1863, Virchow hypothesized that cancer originated at sites of chronic inflammation. Indeed, a growing body of evidence indicates that many malignancies are initiated by infections and chronic inflammation, accounting for over 20% of malignancy cases worldwide. However, the molecular and cellular mechanisms revealing how chronic inflammation leads to tumorigenesis remain largely unknown.[1-3] Human hepatocellular carcinoma (HCC), a primary malignancy of the liver and the third-leading cause of cancer mortality worldwide,[4, 5] is an example of inflammation-induced cancer. In humans, chronic viral hepatitis, metabolic liver diseases, and alcohol abuse cause chronic inflammation; this, in turn, can induce fibrosis, cirrhosis, and cancer.[6, 7] Chemokines and chemokine receptors function in the initiation and maintenance of inflammation and fibrosis[1] and might play a crucial role in the chronic inflammation that leads to tumorigenesis.