ABSTRACT
Hepatic alcohol clearance is a key factor to overcome alcohol hangovers, and over the period, alcohol hangovers may lead to inflammation and oxidative stress. Natural food products with high antioxidant and anti-inflammatory effects might contribute to hepatic alcohol clearance, a hypothesis in this study. The present study aimed to evaluate the influence of turmeric (Curcuma longa L., Zingiberaceae) is an herbal product having antioxidant and anti-inflammatory activities, on alcohol metabolism using binge alcohol drinking rat model. In vivo investigations revealed that pretreatment with turmeric extract enhanced alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities upon binge ethanol (3 g/kg). Additionally, pretreatment with turmeric extract regulated CYP2E1 activity and levels of reactive oxygen species (ROS), Bax, Bcl-2, and inflammatory mediators like IL-1ß, IL-6, and TNF-α. Moreover, turmeric extract upregulated superoxide dismutase, catalase, and glutathione peroxidase activities in liver tissues. Together, these observations shed light on the potential beneficial effects of turmeric extract against acute liver toxicity. The results offer an alternative natural functional food product, turmeric extract, to prevent the negative implications of binge drinking.
ABSTRACT
Little is known about how adhesion molecules on APCs accumulate at immunological synapses. We show here that ICAM-1 on APCs is continuously internalized and rapidly recycled back to the interface after antigen-priming T-cell contact. The internalization rate is high in APCs, including Raji B cells and dendritic cells, but low in endothelial cells. Internalization is significantly reduced by inhibitors of Na(+)/H(+) exchangers (NHEs), suggesting that members of the NHE-family regulate this process. Once internalized, ICAM-1 is co-localized with MHC class II in the polarized recycling compartment. Surprisingly, not only ICAM-1, but also MHC class II, is targeted to the immunological synapse through LFA-1-dependent adhesion. Cytosolic ICAM-1 is highly mobile and forms a tubular structure. Inhibitors of microtubule or actin polymerization can reduce ICAM-1 mobility, and thereby block accumulation at immunological synapses. Membrane ICAM-1 also moves to the T-cell contact zone, presumably through an active, cytoskeleton-dependent mechanism. Collectively, these results demonstrate that ICAM-1 can be transported to the immunological synapse through the recycling compartment. Furthermore, the high-affinity state of LFA-1 on T cells is critical to induce targeted movements of both ICAM-1 and MHC class II to the immunological synapse on APCs.
Subject(s)
Antigen-Presenting Cells/immunology , Immunological Synapses/metabolism , Intercellular Adhesion Molecule-1/metabolism , Lymphocyte Function-Associated Antigen-1/metabolism , Cell Line, Tumor , Cells, Cultured , Dendritic Cells/immunology , Endocytosis , Histocompatibility Antigens Class II/metabolism , Humans , Protein Transport , Sodium-Hydrogen Exchangers , T-Lymphocytes/immunologyABSTRACT
The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function- associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.
