Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis

Wörnle, Markus; Schmid, Holger; Banas, Bernhard; Merkle, Monika; Henger, Anna; Roeder, Maximilian von; Blattner, Simone M.; Bock, Elisabeth; Kretzler, Matthias; Gröne, Hermann Josef; Schlöndorff, Detlef

doi:10.2353/ajpath.2006.050491

Cited by 146 publications

(118 citation statements)

References 57 publications

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“…TLR3 can directly trigger apoptosis in human umbilical vein endothelial cells and cancer cells [29,30]. TLR3 plays a role in the development of hepatitis C-associated glomerulonephritis through the induction of mesangial cell apoptosis [31]. Thus, enhanced TLR3 expression in intrahepatic biliary epithelial cells may play a critical role in the induction and maintenance of inflammation, immune destruction, and/or biliary epithelial cell apoptosis in vivo in diseased liver such as PBC, whereas enhanced TLR3 expression in biliary epithelial cells in CHC may play a critical role for protecting them from hepatitis virus infection.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers

et al. 2008

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“…11,14 To verify this observation in primary mesangial cells, we used Ͼ99% pure mesangial cell cultures isolated from glomerular preparations of C57BL/6 mice as described in Materials and Methods. As expected, incubation with increasing doses of poly I:C RNA induced Il-6 mRNA expression in primary mesangial cells, which peaked at 3 hours after poly I:C RNA stimulation and was maximal at a concentration of 10 g/ml.…”

Section: Poly I:c Rna Induces the Production Of Il-6 And Ifn-␤ In Glomentioning

confidence: 99%

Viral RNA Induces Type I Interferon-Dependent Cytokine Release and Cell Death in Mesangial Cells via Melanoma-Differentiation-Associated Gene-5

Flür¹,

Allam²,

Zecher³

et al. 2009

The American Journal of Pathology

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“…Efforts to interrupt the activation of complement have thus far not been successful in ameliorating the MPGN of TSLP transgenic mice (41), although such measures have been successful in other models of glomerulonephritis (34,36). A very recent and potentially important finding is the demonstration of upregulated expression of the Toll-like receptor 3 in human HCV-associated MPGN (42). This suggests a pathway whereby innate immune recognition of pathogens, perhaps independent of or in conjunction with immune complex deposition, may also initiate the events of HCVassociated glomerulonephritis.…”

Section: Hepatitis C Virus-associated Glomerulonephritismentioning

confidence: 99%

Emerging Paradigms in the Renal Pathology of Viral Diseases

Alpers¹,

Kowalewska²

2007

Clinical Journal of the American Society of Nephrology

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This review considers recent information that illuminates pathogenetic mechanisms that involve three of the major viral infections that cause renal injury in the form of HIV-associated nephropathy, polyoma virus nephropathy, and hepatitis C virus-associated glomerulonephritis.Clin J Am Soc Nephrol 2: S6 -S12, 2007. doi: 10.2215/CJN.00280107 HIV-Associated NephropathyA nephropathy that is associated with HIV infection was identified soon after the epidemic of HIV/AIDS first became recognized in the early 1980s. HIV-associated nephropathy (HIVAN) is a combined glomerular and tubular injury that is characterized by a collapsing glomerulopathy (CG) with collapse of glomerular capillary structures and a striking hyperplasia of podocytes, microcystic transformation of renal tubules, and concomitant and likely nonspecific interstitial inflammation and fibrosis consequent to the glomerular and tubular injuries (Figure 1). From a pathology standpoint, three major areas of investigation have led to a deeper understanding of this lesion.The first of these addresses the issue of whether HIVAN is a direct consequence of viral infection of the renal parenchyma or is a secondary consequence of systemic infection. Cohen et al.(1) first reported the presence of HIV RNA in podocytes as revealed by in situ hybridization (ISH) in 1989, a finding that was supported by microdissection studies of Kimmel et al. (2). These studies were difficult to validate because of the failure of others to replicate these findings using conventional techniques of ISH, the inability to demonstrate the presence of viral peptides in renal parenchymal cells by immunohistochemistry, and the inability to demonstrate appropriate receptors for viral entry into cells, namely CD4 and the chemokine receptors CXCR4 or CCR5, on renal parenchymal cells (3). This created a conundrum in that a mechanism for viral entry into renal cells could not be defined. Some but not all of the difficulties were resolved by a more sophisticated form of ISH, which is based on a technique that detects forms of viral DNA that are characteristic of replicating virus (4 -6). With these techniques, it was possible to substantiate the findings of Cohen et al. and convincingly demonstrate HIV infection of podocytes and tubular epithelial cells.A second key development concomitant with the demonstration of HIV infection of human renal epithelial cells was the development of murine models of HIVAN. The best studied of these involves the Tg26 mouse: Mice are made transgenic for a nearly whole-length HIV virus but with a deletion of HIV gag and pol genes to render the virus nonreplicative (7). Studies of these mice, largely by the group of Klotman and their collaborators, have established that expression of HIV genes, presumably modeling the events of renal HIV infection, is sufficient to produce a renal injury in the mouse that is similar to HIVAN in humans. Studies in which kidneys from transgenic mice were transplanted into wild-type controls demonstrated that renal expression of HIV gene...

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Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis

Abstract: Hepatitis C virus (HCV) infection is frequentlyHepatitis C virus infection (HCV) is a major problem worldwide, frequently complicated by a virus-associated glomerulonephritis. During the course of infection, immune complexes and viral RNA reach the mesangium.

Cited by 146 publications

References 57 publications

Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers

Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers

Viral RNA Induces Type I Interferon-Dependent Cytokine Release and Cell Death in Mesangial Cells via Melanoma-Differentiation-Associated Gene-5

Emerging Paradigms in the Renal Pathology of Viral Diseases

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