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The direct profibrotic and indirect immune antifibrotic balance of blocking the cannabinoid 2 receptor


, : The direct profibrotic and indirect immune antifibrotic balance of blocking the cannabinoid 2 receptor. American Journal of Physiology. Gastrointestinal and Liver Physiology 302(12): G1364-G1372

Cannabinoid 2 (CB2) receptors expressed on immune cells are considered to be antifibrogenic. Hepatic stellate cells (HSCs) directly interact with phagocytosis lymphocytes, but the nature of this interaction is obscure. We aimed to study the effects of CB2 receptors on hepatic fibrosis via their role in mediating immunity. Hepatic fibrosis was induced by carbon-tetrachloride (CCl4) administration in C57BL/6 wild-type (WT) and CB2 knockout (CB2–/–) mice. Irradiated animals were reconstituted with WT or CB2–/– lymphocytes. Lymphocytes from naïve/fibrotic WT animals and healthy/cirrhotic hepatitis C virus were preincubated in vitro with or without CB2 antagonist, evaluated for proliferation and apoptosis, and then cocultured with primary mouse HSCs or a human HSC line (LX2), respectively. Lymphocyte phagocytosis was then evaluated. Following CCl4-administration, CB2–/– mice developed significant hepatic fibrosis but less necroinflammation. WT mice harbored decreased liver CD4+ and NK+ cells but increased CD8+ subsets. Naïve CB2–/– mice had significantly decreased T cell subsets. Adoptive transfer of CB2–/– lymphocytes led to decreased fibrosis in the irradiated WT recipient compared with animals receiving WT lymphocytes. Moreover, necroinflammation also tended to decrease. In vitro, a CB2-antagonist directly increased human HSC activation and increased apoptosis and decreased proliferation of mice/human T cells (healthy/fibrotic) and their phagocytosis. We concluded that CB2–/– lymphocytes exert an antifibrotic activity, whereas lack of CB2 receptor in HSCs promotes fibrosis. These findings broaden our understanding of cannabinoid signaling in hepatic fibrosis beyond their activity solely in HSCs.

US$19.90

PMID: 22517772

DOI: 10.1152/ajpgi.00191.2011


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Tyutin, M.G., 1935: Selection of sweet potatoes. In view of the self-sterility characteristic of the sweet potato the floral biology assumes great importance for breeding and the available knowledge on the subject is reviewed in detail. The pollen is usually fertile and the failure to form fruit...

Fyfe W.S., 1983: Subduction and the geochemical cycle. The present balance of crust creation at ocean ridges and above subduction zones appears to be similar to crust removal processes at subduction zones. Almost 10% of the mass of the upper mantle has been influenced by surface hydrosphere, atmospher...

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Coca, A., 2016: Physician knowledge and attitudes on the clinical evaluation and treatment of resistant hypertension: The RESIST study. Resistant hypertension (RH) is associated with a high risk of cardiovascular and renal complications. The purpose of this study was to assess the knowledge and attitudes of Primary Care physicians, general medicine doctors, and clinical cardiologi...

Petros A.M.; Gemmecker G.; Neri P.; Olejniczak E.T.; Nettesheim D.; X.R.X.; Gubbins E.G.; Smith H.; Fesik S.W., 1992: Nmr studies of a fk 506 analog u carbon 13 ascomycin bound to fk 506 binding protein. Multidimensional, heteronuclear NMR methods were used to determine the complete 1H and 13C resonance assignments for [U-13C]ascomycin bound to recombinant FKBP, including stereospecific assignment of all 22 methylene protons. The conformation of a...

Fisher, A.D.; Warde, C., 1983: Technique for real-time high-resolution adaptive phase compensation. An "all-optical" approach for the realization of adaptive optical systems potentially containing in excess of a million spatial-resolution elements is reported. A phase-measurement and -compensation technique called an interference phase...

Keser, I.; Suyani, E.; Aki, S.Zeynep.; Sucak, A.Gulsan.Turkoz., 2014: The positive impact of regular exercise program on stem cell mobilization prior to autologous stem cell transplantation. The present study was planned to determine the effects of regular exercise program on hematopoietic stem cell (HSC) mobilization prior to autologous stem cell transplantation. Twenty-two consecutive patients were enrolled in the study. A regular 2...

Bogousslavsky, J., 1985: Manifestations of pontine hemorrhage. Neurology 35(10): 1528-1528

Liu, J.; Li, S.Cheng.; Luo, X., 2014: Iterative reweighted noninteger norm regularizing SVM for gene expression data classification. Support vector machine is an effective classification and regression method that uses machine learning theory to maximize the predictive accuracy while avoiding overfitting of data. L2 regularization has been commonly used. If the training dataset...

Hughes R.E., 1986: Trace element composition of obsidian butte imperial county california usa. Non-destructive energy dispersive x-ray fluorescence analyses were performed on rhyolitic volcanic glass (obsidian) from Obsidian Butte, located at the south end of the Salton Sea in Imperial County, California. Sixteen trace and rare earth elemen...