Home About us Contact
|
Home About us Contact | ||
|
|
||
Hepatic Cells (hepatic + cell)
Selected AbstractsExpression of caveolin-1 in hepatic cells increases oxidized LDL uptake and preserves the expression of lipoprotein receptors,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2009To Quyen Truong Abstract Oxidized LDL (OxLDL) that are positively associated with the risk of developing cardiovascular diseases are ligands of scavenger receptor-class B type I (SR-BI) and cluster of differentiation-36 (CD36) which can be found in caveolae. The contribution of these receptors in human hepatic cell is however unknown. The HepG2 cell, a human hepatic parenchymal cell model, expresses these receptors and is characterized by a very low level of caveolin-1. Our aim was to define the contribution of human CD36, SR-BI, and caveolin-1 in the metabolism of OxLDL in HepG2 cells and conversely the effects of OxLDL on the levels/localization of these receptors. By comparing mildly (M)- and heavily (H)-OxLDL metabolism between control HepG2 cells and HepG2 cells overexpressing CD36, SR-BI, or caveolin-1, we found that (1) CD36 increases M- and H-OxLDL-protein uptake; (2) SR-BI drives M-OxLDL through a degradation pathway at the expense of the cholesterol ester (CE) selective uptake pathway; (3) caveolin-1 increases M- and H-OxLDL-protein uptake and decreases CE selective uptake from M-OxLDL. Also, incubation with M- or H-OxLDL decreases the levels of SR-BI and LDL-receptor in control HepG2 cells which can be overcome by caveolin-1 expression. In addition, OxLDL move CD36 from low to high buoyant density membrane fractions, as well as caveolin-1 in cells overexpressing this protein. Thus, hepatic caveolin-1 expression has significant effects on OxLDL metabolism and on lipoprotein receptor levels. J. Cell. Biochem. 108: 906,915, 2009. © 2009 Wiley-Liss, Inc. [source] Hepatitis C virus,infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells,HEPATOLOGY, Issue 1 2008Takashi Ebihara Dendritic cell maturation critically modulates antiviral immune responses, and facilitates viral clearance. Hepatitis C virus (HCV) is characterized by its high predisposition to persistent infection. Here, we examined the immune response of human monocyte-derived dendritic cells (MoDCs) to the JFH1 strain of HCV, which can efficiently replicate in cell culture. However, neither HCV RNA replication nor antigen production was detected in MoDCs inoculated with JFH1. None of the indicators of HCV interacting with MoDCs we evaluated were affected, including expression of maturation markers (CD80, 83, 86), cytokines (interleukin-6 and interferon-beta), the mixed lymphocyte reaction, and natural killer (NK) cell cytotoxicity. Strikingly, MoDCs matured by phagocytosing extrinsically-infected vesicles containing HCV-derived double-stranded RNA (dsRNA). When MoDCs were cocultured with HCV-infected apoptotic Huh7.5.1 hepatic cells, there was increased CD86 expression and interleukin-6 and interferon-beta production in MoDCs, which were characterized by the potential to activate NK cells and induce CD4+ T cells into the T helper 1 type. Lipid raft-dependent phagocytosis of HCV-infected apoptotic vesicles containing dsRNA was indispensable to MoDC maturation. Colocalization of dsRNA with Toll-like receptor 3 (TLR3) in phagosomes suggested the importance of TLR3 signaling in the MoDC response against HCV. Conclusion: The JFH1 strain does not directly stimulate MoDCs to activate T cells and NK cells, but phagocytosing HCV-infected apoptotic cells and their interaction with the TLR3 pathway in MoDCs plays a critical role in MoDC maturation and reciprocal activation of T and NK cells. (HEPATOLOGY 2008.) [source] Alcohol potentiates hepatitis C virus replicon expressionHEPATOLOGY, Issue 1 2003Ting Zhang Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-,) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression. We determined whether alcohol enhances HCV RNA expression in the replicon containing hepatic cells. Alcohol, in a concentration-dependent fashion, significantly increased HCV replicon expression. Alcohol also compromised the anti-HCV effect of IFN-,. Investigation of the mechanism(s) responsible for the alcohol action on HCV replicon indicated that alcohol activated nuclear factor ,B (NF-,B) promoter. Caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-,B, abolished alcohol-induced HCV RNA expression. In addition, naltrexone, an opiate receptor antagonist, abrogated the enhancing effect of alcohol on HCV replicon expression. In conclusion, alcohol, probably through the activation of NF-,B and the endogenous opioid system, enhances HCV replicon expression and compromises the anti-HCV effect of IFN-,. Thus, alcohol may play an important role in vivo as a cofactor in HCV disease progression and compromise IFN-,-based therapy against HCV infection. [source] Earlier expression of the transcription factor HFH-11B diminishes induction of p21CIP1/WAF1 levels and accelerates mouse hepatocyte entry into S-phase following carbon tetrachloride liver injuryHEPATOLOGY, Issue 6 2001Xinhe Wang Partial hepatectomy (PH) or toxic liver injury induces the proliferation of terminally differentiated hepatic cells to regenerate the original size of the adult liver. Previous PH liver regeneration studies showed that premature transgenic expression of the Forkhead Box M1b (FoxM1b, HFH-11B) transcription factor accelerated hepatocyte entry into DNA replication (S-phase). In this study, we used carbon tetrachloride (CCl4) liver injury to induce a different type of mouse liver regeneration and show that premature hepatic HFH-11B levels also accelerate the onset of hepatocyte S-phase in this injury model. Unlike PH liver regeneration, earlier hepatocyte proliferation after CCl4 liver injury is correlated with diminished transgenic hepatic levels of p21CIP1/WAF1 at the G1/S transition of the cell cycle. Differential hybridization of cDNA arrays and RNase protection studies determined that CCl4 regenerating liver of transgenic mice displayed early stimulated expression of the S-phase promoting cyclin D1 and cyclin E and sustained levels of Cdc25a phosphatase genes. Compared with previous PH liver regeneration studies, our data suggest that premature expression of HFH-11B activates distinct S-phase promotion pathways in the CCl4 liver injury model. Although proliferating transgenic hepatocytes induced by either PH or CCl4 liver injury displayed early expression of identical M-phase cyclin genes (cyclin B1, B2, A2, and F), only CCl4 regenerating transgenic liver exhibited earlier expression of the M-phase promoting Cdc25b. These studies suggest that CCl4 injury of transgenic liver not only uses the same mechanisms as PH to mediate accelerated hepatocyte entry into mitosis, but also promotes M-phase entry by stimulating Cdc25b expression. [source] Isolation and characterization of epithelial progenitor cells from human fetal liverHEPATOLOGY RESEARCH, Issue 1 2008Yi-Nan Liu Aim:, Hepatic progenitor cells can serve as an alternative source of hepatocytes for the treatment of liver diseases. Methods:, We isolated and expanded the epithelial progenitor cells (EPC) from the human fetal liver and investigated the differentiation of EPC into hepatic cells by fluorescence-activated cell sorter (FACS), real-time polymerase chain reaction (PCR), immunofluorescence assay, western blotting, and periodic acid,Schiff staining. Results:, Isolated EPC possessed highly proliferative ability and subpassaged for more than 25 passages. Real-time PCR showed that EPC expressed liver epithelial markers (cytokeratin [CK]8 and CK18) and biliary-specific markers (CK7 and CK19). FACS analysis indicated that these cells were positive for CD117, CD147, CD90, CD44, human leucocyte antigen class I and CD71, but negative for CD34 and CD45. The EPCpossessed multipotential indicated by differentiating into osteoblasts and adipocytes; when subjected to the hepatic differentiation condition, EPC could be induced to hepatocyte-like cells, which expressed albumin, alpha-fetoprotein, and CK18 proteins. Two months after EPC transplantation, we observed that the grafted cells differentiated into hepatocyte-like cells and there was no observable tumor mass. Conclusion:, We have isolated and characterized the human fetal liver-derived EPC and these cells may serve as an ideal cell source for cell-replacement therapy of diseased livers. [source] Down-regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinomaHISTOPATHOLOGY, Issue 5 2008C J Kim Aims:, ,-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. Methods and results:, Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum ,-fetoprotein level. Conclusions:, The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations. [source] Mutagenicity and Safety Evaluation of Water Extract of,Coriander sativum,LeavesJOURNAL OF FOOD SCIENCE, Issue 1 2010Mariana Ramírez Reyes ABSTRACT:, Coriander has been used as a spice and medicinal plant for centuries. Several studies have described its biological properties and some reports have indicated its pharmacological actions in some human pathology. However, data on its toxicity and metabolism are limited or null, and no research has been conducted with mammalian cells. The purpose of this study was to evaluate the mutagenicity and safety of,Coriandrum sativum,extract. The mutagenic effects of,C. sativum,extract were evaluated by Ames test. Mutagenicity was present when the,C. sativum,extract was used in high concentrations in both tested strains (Salmonella typhimurium,TA97 and TA102). Our research showed that,C. sativum,extract reduced the cell survival of human cell lines (WRL-68 and 293Q cells) by inducing apoptosis and necrosis in the cases where extract concentration was the highest. The,C. sativum,extract altered the cell cycle; it increased the G1 phase of hepatic cells and reduced the G2+M phase in both cell lines in a dose-response manner. These results showed correlation with a reduction in the mitotic index. The extract also induced severe malformations during embryonic development. Exposure of chicken embryos to the,C. sativum,extract resulted in a dose-dependent increase of anomalies. Present results show that,C. sativum,extract reduced the axial skeleton and affected the neural tube, the somites, the cardiovascular structures, and the eye. According to the present results, the,C. sativum,aqueous extract cannot be considered safe. These results indicate that some significant adverse effects of,C. sativum,extract could be observed,in vivo. [source] Regulatory effects of senescence marker protein 30 on the proliferation of hepatocytesPATHOLOGY INTERNATIONAL, Issue 7 2001Terunobu Ishigami Senescence marker protein 30 (SMP 30) is preferentially expressed in the liver. One of its remarkable functions is the protection of cells against various injuries by enhancement of membrane calcium-pump activity. We analyzed the role of SMP 30 in hepatocyte proliferation. SMP 30 expression was decreased initially, then increased along with hepatic regeneration, after carbon tetrachloride (CCl4) administration. SMP 30 expression was decreased in the necrotic phase and then gradually increased. Its increase was slightly delayed just after the mitotic phase. These results lead us to speculate that mitoses of hepatic cells induce enhanced SMP 30 expression. In contrast, administration of lead nitrate (LN) as a hepatic mitogen induced a more stable increase of SMP 30 expression. To estimate the effect of SMP 30 on cell proliferation, we evaluated hepatic mitosis in wild-type and SMP 30-deficient knockout (KO) mice after CCl4 administration. We found an increase in mitotic numbers in hepatocytes of KO mice. This result suggests that SMP 30 has a suppressive effect on cell proliferation. Suppressive activity of SMP 30 cDNA was shown in cultured hepatoblastic cells. Our results suggest that SMP 30 performs a regulatory function in liver regeneration. [source] Immunohistochemical and scanning electron microscopic comparison of the collagen network constructions between pig, goat and chicken liversANIMAL SCIENCE JOURNAL, Issue 4 2009Shotaro NISHIMURA ABSTRACT The distribution and three-dimensional architecture of collagen fibers were compared between pig, goat and chicken livers. Immunohistochemical staining revealed that collagen type I was identified in the interlobular connective tissue region and intralobular areas in pigs and goats. Type III collagen was also identified in the interlobular connective tissue region and intralobular sinusoidal walls. In the chicken liver, only the circumference region of the vessels was immunostained with collagen type I and III antibodies and the interlobular connective tissue wall could not be distinguished clearly. In the intralobular region, collagen type I antibody immunoreacted around the hepatic cells but collagen type III antibody immunoreacted weakly. In the NaOH macerated specimen, well-developed collagen bundles formed the prominent interlobular walls in pigs. In contrast, the wall in the goat liver comprised a thin layer of the bundles. In the chicken liver, there were no notable collagen septa between lobules. The intralobular collagen construction was quite different between the animals, indicating a fragile collagen fibril networks in pigs, a robust framework in goats and dense fabric-like septa in chickens. These results indicate that the distinct collagen frameworks may contribute to the histological strength of the livers in each of the animal species. [source] Homing of transplanted bone marrow cells in livers of Schistosoma mansoni -infected miceAPMIS, Issue 4 2010NAGWA ELKHAFIF Elkhafif N, Voss B, Hammam O, Yehia H, Mansy S, Akl M, Boehm S, Mahmoud S, El Bendary O, El Fandy G. Homing of transplanted bone marrow cells in livers of Schistosoma mansoni -infected mice. APMIS 2010; 118: 277,87. The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its importance in physiopathological processes is still debated. Murine schistosomiasis was used as a liver injury model and unfractionated male mice BMCs were transplanted through intrahepatic injection into non-irradiated Schistosoma mansoni -infected female mice on their 16th week post-infection. Two weeks after bone marrow transplantation, mice were sacrificed on a weekly basis until 10 weeks. Tracing of male donor-derived cells in female recipient mice livers was carried out by the detection of Y chromosome expression by fluorescent in situ hybridization (FISH) and also of chromodomain Y-linked (CDYL) protein by indirect immunofluorescence (IF). Their transformation into hepatocytes was studied by double labelling indirect IF using antibodies directed against CDYL and mouse albumin. Histopathological and electron microscopic examinations revealed the presence of small hepatocyte-like cells in the periportal tracts and in between the hepatocytes facing the sinusoids. Donor-derived cells showing Y chromosome by FISH and expressing CDYL protein by IF were recovered in the infected transplanted livers. The initial number of these cells increased with increased post-transplantation time. Cells were mainly localized in the periphery of schistosoma granuloma. Few donor-derived cells appeared within the hepatic parenchymal tissue and showed positivity for albumin secretion by double labelling with IF. We suggest that transplanted bone marrow stem cells can repopulate the Schistosoma -infected liver of immunocompetent mice. Their differentiation is a complex event controlled by many factors and needs to be further characterized extensively. The extent and type of liver injury and the number of transplanted cells are important variables in the process of stem cell engraftment and differentiation into functioning hepatic cells that still need to be defined. [source] Perfluorocarbon facilitated O2 transport in a hepatic hollow fiber bioreactorBIOTECHNOLOGY PROGRESS, Issue 5 2009Guo Chen Abstract A mathematical model describing O2 transport in a hepatic hollow fiber (HF) bioreactor supplemented with perfluorocarbons (PFCs) in the circulating cell culture media was developed to explore the potential of PFCs in properly oxygenating a bioartificial liver assist device (BLAD). The 2-dimensional model is based on the geometry of a commercial HF bioreactor operated under steady-state conditions. The O2 transport model considers fluid motion of a homogeneous mixture of cell culture media and PFCs, and mass transport of dissolved O2 in a single HF. Each HF consists of three distinct regions: (1) the lumen (conducts the homogeneous mixture of cell culture media and PFCs), (2) the membrane (physically separates the lumen from the extracapillary space (ECS), and (3) the ECS (hepatic cells reside in this compartment). In a single HF, dissolved O2 is predominantly transported in the lumen via convection in the axial direction and via diffusion in the radial direction through the membrane and ECS. The resulting transport equations are solved using the finite element method. The calculated O2 transfer flux showed that supplementation of the cell culture media with PFCs can significantly enhance O2 transport to the ECS of the HF when compared with a control with no PFC supplementation. Moreover, the O2 distribution and subsequent analysis of ECS zonation demonstrate that limited in vivo-like O2 gradients can be recapitulated with proper selection of the operational settings of the HF bioreactor. Taken together, this model can also be used to optimize the operating conditions for future BLAD development that aim to fully recapitulate the liver's varied functions. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] | |||||||||||||||||||||||||