Targeting dexamethasone to Kupffer cells: Effects on liver inflammation and fibrosis in rats

Melgert, Barbro N.

doi:10.1053/jhep.2001.27805

Cited by 103 publications

(72 citation statements)

References 53 publications

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“…The ED1-positive macrophages observed in the fibrotic areas, in which infiltration might be affected with MIF produced in degenerated hepatocytes, may be associated with the development of myofibroblast-like cells, at least in part, because such macrophages can produce TNF-α and TGF-β (Khalil et al 1989;Leist et al 1995). It has been reported that Kupffer cells, resident macrophages, are considered to be responsible for progression of hepatic fibrosis (Luckey and Petersen, 2001;Melgert et al 2001). Thus, the association of resident macrophages with MIF expression should be investigated in further studies.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide

Hori

Sato²,

Yamate³

et al. 2009

Eur J Histochem

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Macrophage migration inhibitory factor (MIF) is a molecule known to regulate macrophage accumulation at sites of inflammation. To elucidate the role of MIF in progression of liver fibrosis, the immunohistochemical localization of MIF and macrophages in the liver were examined. Male Wistar rats received thioacetamide (TA) injections (200 mg/kg, i.p.) for 1 or 6 weeks. In biochemical and histological tests, it was confirmed that liver fibrosis was induced. In immunohistochemical analyses, the expression of MIF protein was seen in hepatocytes in the areas extending out from the central veins to the portal tracts. In particular, at 6 weeks, immunoreactivity was detected in degenerated hepatocytes adjacent to the fibrotic areas but hardly observed in the fibrotic areas. On the other hand, a number of exudate macrophages stained by antibody ED1 were seen in the areas from the central veins to the portal tracts at 1 week and in the fibrotic areas at 6 weeks. Macrophages also showed a significant increase in number as compared with controls. These results revealed that there was a close relationship between the appearance of MIF expression and ED1-positive exudate macrophages in degenerated hepatocytes during the progression of TA-induced liver fibrosis

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide

Hori

Sato²,

Yamate³

et al. 2009

Eur J Histochem

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show abstract

“…With continued refinements, however, liver slices again offer some unique advantages (664,668) and have more recently been used to test drug targeting methods (410,411), antifibrotic therapies (224), and cell fate during injury and repair following exposure to hepatotoxins (221). The slice technology can be complemented with either real-time PCR for stellate cell-specific genes (665) or laser-capture microdissection to enrich for stellate cells recovered from within the slice.…”

Section: Other Models: Liver Slices In Vivo Methodsmentioning

confidence: 99%

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,419

2,549

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The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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“…34 Similarly, dexamethasone, coupled to mannosylated albumin (Dexa(5)-Man(10)-HSA), specifically delivered to Kupffer cells, reduced inflammation and liver damage. 35 On the contrary, nonspecific activation of all immune cells including Kupffer cells is a hallmark of autoimmune human diseases. To stimulate immune cells in the liver, concanavalin A can be applied intraperitoneally.…”

Section: Targeting Kupffer Cellsmentioning

confidence: 99%

“…Experimental approaches against TNFa in models of liver fibrosis have shown reduction of liver injury. 34,35,88 TNFa in liver, mainly produced by Kupffer cells, 89 binds to TNFa receptors (TNFR) on hepatocytes and Kupffer cells after its release. ADAM17 is a key player in this signaling, and mice lacking ADAM17 specifically in myeloid lineage release almost no TNFa into serum after lipopolysaccharide application.…”

Section: Mmps In Recovery Of Liver Fibrosismentioning

confidence: 99%

Metalloproteinases in liver fibrosis: current insights

Zbodakova¹,

Chalupský²,

Turečková³

et al. 2017

MNM

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Liver fibrosis is defined by excessive deposition of extracellular matrix. The fibrotic conditions result from the imbalance between synthesis and deposition of fibrous tissues and decomposition of these matrix proteins. This process can be reversed as a regular part of the healing process after hepatic damage or can become chronic. When the protein matrix synthesis predominates and the decomposition is suppressed, fibrosis will progress into irreversible cirrhosis or steatosis. Among the molecular players involved in fibrotic liver diseases, metalloproteinases of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) families are critical in the development of liver fibrosis and its resolution. Previously, MMPs were recognized as extracellular matrix degrading enzymes. Currently, they are also known as mediators in a variety of processes related to immunity and tissue repair. In this article, we have reviewed the models of liver fibrosis and findings on MMPs and ADAMs in hepatic fibrosis conditions.

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Targeting dexamethasone to Kupffer cells: Effects on liver inflammation and fibrosis in rats

Cited by 103 publications

References 53 publications

Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide

Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Metalloproteinases in liver fibrosis: current insights

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