No abstract available.
Human ; Kupffer Cells/*ultrasonography ; Liver Diseases/*pathology

Adult ; Aged ; Carcinoma, Hepatocellular ; pathology ; Female ; Humans ; Immunohistochemistry ; Kupffer Cells ; pathology ; Liver Neoplasms ; pathology ; Male ; Middle Aged

OBJECTIVESTo investigate the relationship between the apoptosis of sinusoidal endothelial cells (SEC) and the hepatocyte injury of the livers after their transplantation into rats.

METHODSMale SD rats were divided into three groups randomly: sham group, UW1h group and UW12 h group. Orthotopic liver transplantations were performed using the technique described by Kamada with a modification. A survival rate curve was made using the Kaplan-Meier method. Liver tissue specimens and blood samples were collected at different time points after the surgeries. Six animals were sacrificed at each time-point. The liver injury was evaluated by serum ALT and HA levels. The incidence of apoptosis in SECs was measured using the Tunel method. Additionally, the typical morphology indication of apoptosis was observed by transmission electron microscopy.

RESULTSThe survival rate at 168 h in the UW12 h group was significantly lower than that in the UW1h group (F = 6.39, P<0.05). The levels of serum ALT and HA were significantly higher in UW12 h group than those in UW1h group (F = 3.99, P<0.05; F = 12.43, P<0.05). The serum ALT level reached its peak at 6 h after transplantation in both groups. The AI of SEC was significantly higher in the UW12 h group than those in the UW1h group and sham group (F = 63.58, P<0.01; F = 86.58, P<0.01). The apoptosis index (AI) in the UW1h group and in the UW12 h group both reached their peak at 6 h postoperatively and the AI of SEC of each group was positively correlated with their serum ALT levels significantly (r = 1.0, P,0.01; r = 0.962, P<0.05).

CONCLUSIONThe increase of apoptosis of SEC is significantly correlated with the dysfunction of the livers after transplantation in rats, and the dysfunction was mainly caused by the process of cold preservation/reperfusion injury.

Animals ; Apoptosis ; physiology ; Cryopreservation ; Endothelial Cells ; pathology ; Hepatocytes ; pathology ; Kupffer Cells ; pathology ; Liver ; pathology ; Liver Transplantation ; adverse effects ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology

Animals ; Disease Progression ; Fatty Liver ; metabolism ; pathology ; Humans ; Inflammation ; Kupffer Cells ; metabolism ; Non-alcoholic Fatty Liver Disease

OBJECTIVES: This study aimed to explore the functions and potential regulatory targets of local macrophages in nonalcoholic fatty liver combined with Porphyromonas gingivalis (P. gingivalis)infection. METHODS: Single-cell RNA sequencing was used to analyze the phenotypes and functional changes in various cells in the liver tissue of nonalcoholic steatohepatitis (NASH) mice fed with P. gingivalis. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and immunofluorescence staining were applied to observe the inflammation and expression levels of macrophage antigen presenting functional markers in the NASH liver. Oil red staining was performed to observe the accumulation of local adipose tissue in the NASH liver. Results were verified through RT-PCRand RNA sequencing using P. gingivalis-lipopolysaccharide treated mouse peritoneal macrophages. RESULTS: In comparison with healthy livers with Kupffer cells, the NASH liver combined with P. gingivalis infection-related macrophages showed significant heterogeneity. C1qb, C1qc, Mafb, Apoe, and Cd14 were highly expressed, but Cd209a, H2-Aa, H2-Ab1, and H2-DMb1, which are related to the antigen presentation function, were weakly expressed. Further in vivo and in vitro investigations indicated that the activation and infiltration of these macrophages may be due to local P. gingivalis-lipopolysaccharide accumulation. CONCLUSIONS P. gingivalis-lipopolysaccharide induces a local macrophage immunotolerance phenotype in nonalcoholic fatty liver, which may be the key mechanism of periodontitis pathogen infection that promotes NASH inflammation and pathogenesis. This study further clarifies the dysfunction and regulatory mechanisms of macrophages in the pathogenesis of P. gingivalis-infected NASH, thereby providing potential therapeutic targets for its clinical treatment.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/pathology* ; Kupffer Cells/pathology* ; Porphyromonas gingivalis ; Lipopolysaccharides/metabolism* ; Inflammation/pathology* ; Macrophages/metabolism* ; Mice, Inbred C57BL

OBJECTIVETo investigate HMGB-1 expression and its extracellular release of cultured primary hepatic parenchymal cells (HC) and Kupffer cells (KC) that were induced by lipopolysaccharides (LPS).

METHODSPrimary hepatic parenchymal cells and Kupffer cells were cultured in flasks, and some cells were treated with 500 microg/L LPS for 24 hours (induced group) and some were not treated with LPS and served as controls. All of the cells were repeatedly frozen-thawed, and the expression levels of HMGB1-mRNA and HMGB1 proteins were detected by semi-quantitative RT-PCR and Western blot respectively. Then HC and KC were subcultured in 24-well culture plates for 6 h, 12 h, 24 h and 48 h, and the HMGB1 protein in culture fluids was detected by Western blot at each time point.

RESULTSCompared with the cells in the control group, the expression levels of HMGB1-mRNA in the induced group were significantly increased in both HC and KC at 24 h (t=31.32 and 45.90, P<0.05) and the protein levels of HMGB1 showed the same results (t=46.19 and 38.44, P<0.05). There was a small quantity of HMGB1 protein in the culture fluids of two control groups and the induced group of HC. However the HMGB1 protein in the induced group of KC were obviously increased with prolonged culture time (F=42.74, P<0.05). Compared with the control group, the level of HMGB1 protein in the induced group of KC was not increased at 6 h (t=9.57, P>0.05) but was significantly increased at 12 h, 24 h and 48 h (t=21.95, 32.39, 44.16, respectively P<0.05).

CONCLUSIONLPS could increase HMGB1 expression of HC and KC and HMGB1 release from KC, but not from HC. The results suggest that KC play an important role in triggering inflammation and liver injury.

Animals ; Cells, Cultured ; Female ; HMGB1 Protein ; metabolism ; Hepatocytes ; metabolism ; Kupffer Cells ; metabolism ; Lipopolysaccharides ; Liver ; cytology ; metabolism ; pathology ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Hepatic fibrosis results from iterative hepatic injury with sustained inflammation, formation of scar tissue, loss of tissue architecture and organ failure. There is no doubt, from both human and animal studies, that too much or too protracted inflammation in the liver leads to excess scarring. During liver injury, Kupffer cells can quickly flood the hepatic milieu with soluble mediators, including oxidants, cytokines, and proteinases, which can affect stellate cell proliferation, migration, and differentiation. On the other hand, the contribution of Kupffer cells to regression of hepatic fibrosis has been demonstrated. These findings underscore the potential importance of hepatic macrophages in regulating both stellate cell biology and extracellular material degradation during regression of hepatic fibrosis. Therefore, biological characterization of Kupffer cells, their interactions with stellate cells in the cytokine environment are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and recovery.
Animals ; Apoptosis ; Hepatic Stellate Cells ; physiology ; secretion ; Hepatocytes ; pathology ; Humans ; Kupffer Cells ; physiology ; secretion ; Liver Cirrhosis ; etiology ; metabolism ; pathology ; Liver Regeneration ; physiology ; Matrix Metalloproteinases, Secreted ; metabolism ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effect of glycine on CD14 and NF-kappa B in Kupffer cells from rat liver grafts after ischemia-reperfusion injury (IRI).

METHODSThe rats were randomly divided into an IRI group, saline solution preconditioning group, and glycine preconditioning group. Their survival rates, graft functions, and hepatic histopathologic examinations were observed after IRI. Kupffer cells (KCs) following IRI were isolated and cultured to detect CD14 mRNA, NF-kappa B binding activity, and the TNF alpha and IL-1 level in the supernatant of the media.

RESULTS(1) Glycine preconditioning greatly enhanced the one-week survival rate (chi2 = 6.67 and 8.57 respectively), improved graft function, and ameliorated the histopathologic signs of injury. (2) The CD14 mRNA expression level (F = 7.64), NF-kappa B binding activity (F = 11.47), TNF alpha and IL-1 production (F = 14.08 and 9.56 respectively) in the glycine group were significantly lower than those in the other two groups.

CONCLUSIONGlycine could efficiently protect rat liver grafts from ischemia-reperfusion injury by repressing the expression of CD14 and NF-kappa B binding activity in Kupffer cells and inhibiting the productions of TNF alpha and IL-1.

Animals ; Cells, Cultured ; Glycine ; pharmacology ; Kupffer Cells ; metabolism ; pathology ; Lipopolysaccharide Receptors ; biosynthesis ; genetics ; Liver ; blood supply ; metabolism ; Liver Transplantation ; adverse effects ; NF-kappa B ; metabolism ; RNA, Messenger ; biosynthesis ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology

The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.
Endothelial Cells/metabolism ; Hepatic Stellate Cells/metabolism ; Humans ; Kupffer Cells/metabolism ; Liver Cirrhosis/metabolism/*pathology ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase Type II/antagonists & inhibitors/genetics/*metabolism ; Polymorphism, Single Nucleotide ; RNA, Untranslated/metabolism

OBJECTIVETo observe the expression change of signal regulatory protein alpha1 (SIRPalpha1) in autoimmune hepatitis (AIH) and approach the relationship between SIRPalpha1 and the extent of inflammation.

METHODSImmunohistochemistry is used to detect the expression of SIRPalpha1 in the paraffin section preparations of 33 AIH and 10 normal hepatic tissue.

RESULTSSIRPalpha1 is positive or weakly positive expressed in AIH. The staining is localized in the cytoplasm of Kupffer cells in the hepatic sinusoid with focal distribution. It is negative in normal hepatic tissue. In light AIH, it is negative or weakly positive expressed with a 36.4 percent of the positive rate (4/11). The positive or strong positive expression is found in the moderate AIH with an 84.2 percent of the positive rate(16/19). There is statistical significance between both light AIH, moderate AIH and severe AIH (P less than 0.001) and moderate AIH and light AIH (P less than 0.001). There is no statistical significance between both light AIH and severe AIH (P = 0.145 ) and moderate AIH and severe AIH (P = 0.084).

CONCLUSIONSAs a negative regulatory factor, the expression of SIRPalpha1 in hepatic sinusoid Kupffer cells is some associated with the extent of AIH.

Adolescent ; Adult ; Aged ; Antigens, Differentiation ; metabolism ; Cell Communication ; Child ; Female ; Hepatitis, Autoimmune ; metabolism ; pathology ; Hepatocytes ; metabolism ; pathology ; Humans ; Kupffer Cells ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Immunologic ; metabolism ; Young Adult