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Recent studies have demonstrated the existence of an intracellular (associated with mitochondria) tumour necrosis factor-α (TNF) binding protein. In an attempt to elucidate if this receptor could be involved in TNF action, we have incubated liver isolated mitochondria in the presence of recombinant murine TNF. The results show that the addition of TNF at concentrations as low as 10 -6 ...
The chemokine, mob-1, is involved in inflammatory and immune responses and may be an important mediator of the inflammatory response in the liver. Here, we investigated the upstream signal pathways that could be involved in the regulation of mob-1 expression. We have found that in primary rat hepatocytes the isolation and subsequent culture of these cells induced mob-1 expression. A similar induction...
Application of tumor necrosis factor (TNF) in combination with galactosamine (GalN) in mice causes severe apoptosis of hepatocytes, resulting in complete destruction of the liver. Administration of high levels of unconjugated bilirubin and abnormally high production of unconjugated bilirubin have been reported to cause liver damage and are associated with several human pathologies. Serum alanine aminotransferase...
The polymorphism at position 25 of the gene encoding transforming growth factor-β1 (TGF-β1), which changes the amino acid sequence of the signal peptide sequence (arginine to proline), is causing a variation in TGF-β1 production. The homozygous genotype (Arg25Arg) is associated with higher TGF-β1 production than the heterozygous (Arg25Pro) genotype. Therefore, the possible involvement of this genetic...
Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism with variable penetrance. Only a minority of C282Y homozygotes develop clinical overt disease and cirrhosis. The phenotypic heterogeneity of HHC may be due to host genetic factors influencing fibrogenesis such as cytokine gene polymorphisms. In this respect, we investigated the impact of functional genetic polymorphisms...
The platelet-derived growth factor (PDGF) family, which regulates many physiological and pathophysiological processes has recently been enlarged by two new members, the isoforms PDGF-C and -D. Little is known about the expression levels of these new members in hepatic fibrosis. We therefore investigated by quantitative real time PCR (Taqman) the mRNA expression profiles of all four PDGF isoforms in...
Chronic elevation of circulating Interleukin-6 (IL-6) is observed in elderly individuals as well as in several illnesses, including chronic kidney diseases. A number of cells and tissues possess the ability to metabolize significant amounts of IL-6 in vitro. However, information on signals and mechanisms by which IL-6 is removed from blood in humans is still incomplete. To assess the individual role...
Hepatitis C virus infection and its associated liver inflammatory disease is a major global health problem affecting over 170 million people worldwide. Following viral infection, multiple pro-inflammatory mediators contribute to recruitment of immune cells to the liver and to the generation of an anti-viral immune response. However, when this vigorous immune response fails to eliminate the virus,...
Pathologies such as liver fibrosis and scleroderma are characterized by harmful levels of transforming growth factor beta 1 (TGFβ1). These levels could be neutralized if inhibitors of this cytokine were available. With this aim we searched for peptides with binding affinity for TGFβ1 using a phage-displayed random 15-mer peptide library. Some peptides thus identified blocked activity of TGFβ1 in vitro,...
Although 17β-estradiol (E2) administration following trauma-hemorrhage (T-H) reduces liver injury by decreasing neutrophil accumulation via estrogen receptor (ER)-α, it remains unclear whether cytokine-induced neutrophil chemoattractant (CINC)-1 production by Kupffer cells (KC) is directly modulated by ER-α under such condition. Male rats underwent laparotomy and hemorrhagic shock (40mmHg for 90min),...
Trypanosoma cruzi (T. cruzi) infected C57BL/6 mice developed a progressive fatal disease due to an imbalance in the profile of circulating related compounds accompanying infection like tumor necrosis factor alpha (TNFα). TNFα has been proposed as an important effector molecule in apoptosis. In this work, we evaluate inflammation and the proteins involved in apoptotic process in liver of infected mice...
Hepatitis C virus is a global health concern, estimated to infect 2–3% of the world’s population. Inter-individual differences in the course of infection and response to therapy, highlighted by recent genomewide association studies, point to the crucial role of the host immune system in the efficient control of infection. Ongoing progress in the studies of the role of innate immunity during hepatitis...
It is already clearly demonstrated that IFN-γ plays important roles in differentiation and maturation of T cells, B cells and macrophages; however, it is not clear whether NK cell development is regulated by IFN-γ. In our study by using IFN-γ-deficient mice (GKO), we observed that the percentage and number of NK1.1 + CD3 − cells were declined significantly in the liver, but not in...
The stromal cell derived factor 1 (SDF-1/CXCL12) plays an essential role in the homing of hematopoietic stem and progenitor cells (HSPCs) to bone marrow (BM). It is not known whether SDF-1 may also regulate the homing of HSPCs to the liver during extramedullary hematopoiesis (EMH). Here, we investigated the possible role of SDF-1 in attracting HSPCs to the liver during experimental EMH induced by...
Interleukin-15 (IL-15) is essential for the homeostasis of lymphoid cells particularly memory CD8+ T cells and NK cells. These cells are abundant in the liver, and are implicated in obesity-associated pathogenic processes. Here we characterized obesity-associated metabolic and cellular changes in the liver of mice lacking IL-15 or IL-15Rα. High fat diet-induced accumulation of lipids was diminished...
IL-15 is a member of the gamma chain family of cytokines (γc – CD132). The IL-15 receptor (IL-15R) complex consists of 3 subunits: the ligand-binding IL-15Rα chain (CD215), the β chain (CD122; also used by IL-2), and the common γ chain. The biological activities of IL-15 are mostly mediated by the IL-15:IL-15Rα complex, produced by the same cell and ‘trans-presented’ to responder cells expressing...
Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and frequently requires liver transplantation. The host immune response has an important role driving fibrosis deposition by activating hepatic stellate cells (HSCs). Interleukin-22 (IL-22) is a cytokine that...
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