Cytokines and chemokines in the immune response to hepatitis C infection

Heydtmann, Mathis; Shields, PL; McCaughan, Geoffrey W.; Adams, David H.

doi:10.1097/00001432-200106000-00006

Cited by 48 publications

(35 citation statements)

References 77 publications

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“…in which within the normal liver hepatic stellate cells 41 and hepatocytes, 42 for example, release chemokines into the space of Dissé, we hypothesize that these chemokines can be taken up by LSEC from the basal side and are then presented on the luminal side, supporting CD4 ϩ T cell trafficking. Transmigrating T cells might rapidly remigrate, receive suppressive signals upon transmigration, 43,44 or subsequently interact with tolerogenic Ito cells.…”

Section: Discussionmentioning

confidence: 83%

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

et al. 2008

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Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface. In the present study, we investigated whether liver sinusoidal endothelial cells ( H omeostatic extravasation into the liver parenchyma and transmigration of T cells into sites of inflammation under pathological conditions such as hepatitis and cholangitis are mediated by multiple steps involving activation and firm adhesion followed by egress. The process is closely regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the cell surface. 1,2 Within the liver, lymphocyte adhesion, a prerequisite for transmigration, occurs mainly within the sinusoidal circulation. Thus, T cell immigration into the liver is presumed to happen predominantly via the sinusoids. 3 Liver sinusoidal endothelial cells (LSEC) lining the sinusoids form a morphologically and functionally distinct endothelium that lacks a basement membrane, fails to form tight junctions, and displays fenestrae grouped to sieve plates. 4 In contrast to other tissues, selectins are not necessary for the initial adhesion of leukocytes to the liver microvasculature. The

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Section: Discussionmentioning

confidence: 83%

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

et al. 2008

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“…Our results suggest a role for immune-mediated apoptosis of hepatocytes by infiltrating T cells. HCV infection induces T cell response and a number of inflammatory mediators, including cytokines and chemokines (32). It has demonstrated that TRAIL expression is up-regulated in T cells activated by anti-CD3 (19,25,33,34).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Core Protein Modulates TRAIL-Mediated Apoptosis by Enhancing Bid Cleavage and Activation of Mitochondria Apoptosis Signaling Pathway

Chou

Tsai

et al. 2005

The Journal of Immunology

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Hepatitis C virus (HCV) is a major human pathogen causing chronic liver disease, which leads to cirrhosis of liver and hepatocellular carcinoma. The HCV core protein, a viral nucleocapsid, has been shown to affect various intracellular events, including cell proliferation and apoptosis. However, the precise mechanisms of the effects are not fully understood. In this study, we show that HCV core protein sensitizes human hepatocellular carcinoma cell line, Huh7, conferred sensitivity to TRAIL-, but not Fas ligand-mediated apoptosis. Huh7 cells are resistant to TRAIL, despite the induction of caspase-8 after TRAIL engagement. However, HCV core protein induces TRAIL apoptosis signaling via sequential induction of caspase-8, Bid cleavage, activation of mitochondrial pathway, and effector caspase-3. HCV core protein also induces activation of caspase-9 after TRAIL engagement, and the induction of TRAIL sensitivity by HCV core protein could be reversed by caspase-9 inhibitor. Therefore, the HCV core protein-induced TRAIL-mediated apoptosis is dependent upon activation of caspase-8 downstream pathway to convey the death signal to mitochondria, leading to activation of mitochondrial signaling pathway and breaking the apoptosis resistance. These results combined indicate that the HCV core protein enhances TRAIL-, but not Fas ligand-mediated apoptotic cell death in Huh7 cells via a mechanism dependent on the activation of mitochondria apoptosis signaling pathway. These results suggest that HCV core protein may have a role in immune-mediated liver cell injury by modulation of TRAIL-induced apoptosis.

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“…CCL5/CCR5 interaction is likely to be important during hepatitis C virus infection, where T cells are recruited to the liver parenchyma to mediate clearance of HCVinfected hepatocytes 95 . Consistent with this hypothesis, RANTES-403 G/A SNP was observed to decrease risk of severe inflammation in Hepatitis C virus-seropositive patients heterozygous or homozygous for the RANTES promoter alleles -403*A 96,72 .…”

Section: Other Diseasesmentioning

confidence: 99%

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

Navratilova¹

2006

BIOMED PAP

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Cytokines and chemokines in the immune response to hepatitis C infection

Cited by 48 publications

References 77 publications

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

Hepatitis C Virus Core Protein Modulates TRAIL-Mediated Apoptosis by Enhancing Bid Cleavage and Activation of Mitochondria Apoptosis Signaling Pathway

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

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