Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with histological activity of liver disease

Apolinario, A.; Alvarez-Perez, E.; Saez, Alicia; Lozano, Carlos; Vargas, Javier; García‐Monzón, Carmelo

doi:10.1016/s0168-8278(02)80789-9

Cited by 56 publications

(97 citation statements)

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“…CXCR3 ligands were detected on inflamed hepatic endothelium at sites of lymphocyte infiltration and also on inflamed bile ducts and proliferating bile ductules. These observations are consistent with studies in chronic hepatitis C showing increased expression of CXCR3 ligands and CXCL10 mRNA on hepatocytes at sites of interface hepatitis 26,39,42,43 but suggest that CXCR3 ligands are induced at sites of lymphocyte infiltration in chronic hepatitis regardless of the underlying cause. We compared levels of the CXCR3 receptor on LILs isolated from normal liver and a variety of chronic inflammatory liver diseases.…”

Section: Discussionsupporting

confidence: 90%

CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

Curbishley¹,

Eksteen²,

Gladue³

et al. 2005

The American Journal of Pathology

120

134

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Section: Discussionsupporting

confidence: 90%

CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

Curbishley¹,

Eksteen²,

Gladue³

et al. 2005

The American Journal of Pathology

120

134

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“…However, these data do not exclude that the chemokine levels in the liver may vary during the course of HCVrelated liver disease, as demonstrated by others [32] . Indeed, a statistically significant association between the intrahepatic RANTES expression and the inflammatory activity of chronic hepatitis C was found [32] .…”

Section: Discussionmentioning

confidence: 69%

“…Indeed, a statistically significant association between the intrahepatic RANTES expression and the inflammatory activity of chronic hepatitis C was found [32] .…”

Section: Discussionmentioning

confidence: 99%

Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis

Nahon¹

2008

WJG

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“…1,2 In hepatitis C virus (HCV)-infected liver RANTES messenger RNA has been shown to be up-regulated, and its intrahepatic expression levels correlate with serum alanine aminotransferase activities. 3,4 Furthermore, expression of full-length HCV complementary DNA induces the expression of RANTES in hepatocyte cell lines, 5 possibly mediated through activation of nuclear factor B. 6 Interestingly, a 32-base pair deletion in the gene of the CC chemokine receptor 5 (CCR5 ⌬32), which results in decreased receptor expression, 7 has recently been linked to a negative response to interferon monotherapy in hepatitis C. 8 Because the CCR5 ligand RANTES preferentially attracts T helper 1 lymphocytes, 9 RANTES might also be associated with treatment response to antiviral therapy, which is thought to depend on a sufficient proinflammatory cytokine response.…”

mentioning

confidence: 99%

Haplotype-taggingRANTES gene variants influence response to antiviral therapy in chronic hepatitis C

et al. 2004

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The response to antiviral therapy for chronic hepatitis C virus (HCV) is complex and is determined by both environmental and genetic factors. Recently, interacting gene polymorphisms of the chemokine RANTES have been shown to affect HIV disease progression. Our aim was to assess if these RANTES variants are associated with response to anti-HCV therapy. Three linked RANTES single nucleotide polymorphisms (403 G/A, Int1.1 T/C, and 3 222 T/C) were determined in 297 Caucasian patients who were treated for chronic HCV infection and 152 control subjects. Characteristic nucleotide combinations on single chromosomes (haplotypes) were reconstructed and tested for disease association. Four common RANTES haplotypes (prevalence 73%) were identified in patients and controls. There was a strong association of RANTES haplotype distribution with outcome of antiviral combination therapy (P ‫؍‬ .007). Specifically, RANTES haplotypes carrying Int1.1 C and 3 222 C alleles were more frequent in nonresponders than in patients with a sustained response to antiviral therapy (odds ratio 1.9, P ‫؍‬ .01). The influence of these RANTES haplotypes on the outcome of therapy was more pronounced in patients infected with HCV genotypes 1 and 4 (odds ratio 2.3, P ‫؍‬ .02). Because RANTES haplotypes carrying Int1.1 C are known to down-regulate RANTES transcriptional activity in vitro, the haplotype analysis fits the hypothesis of a diminished T helper 1 lymphocyte response in patients with a negative response to antiviral therapy. In conclusion, RANTES haplotypes might contribute to the polygenic interaction between HCV and the host immune system and could help to risk stratify patients prior to antiviral therapy. ( T he CC chemokine RANTES (regulated on activation normally T cell expressed and secreted; systematic name CCL5) attracts T lymphocytes to inflamed tissues and is produced by T lymphocytes, monocytes, fibroblasts, and endothelial cells. 1,2 In hepatitis C virus (HCV)-infected liver RANTES messenger RNA has been shown to be up-regulated, and its intrahepatic expression levels correlate with serum alanine aminotransferase activities. 3,4 Furthermore, expression of full-length HCV complementary DNA induces the expression of RANTES in hepatocyte cell lines, 5 possibly mediated through activation of nuclear factor B. 6 Interestingly, a 32-base pair deletion in the gene of the CC chemokine receptor 5 (CCR5 ⌬32), which results in decreased receptor expression, 7 has recently been linked to a negative response to interferon monotherapy in hepatitis C. 8 Because the CCR5 ligand RANTES preferentially attracts T helper 1 lymphocytes, 9 RANTES might also be associated with treatment response to antiviral therapy, which is thought to depend on a sufficient proinflammatory cytokine response. 10,11 The human RANTES gene spans 8.5 kb on chromosome 17q11-q12 and has the characteristic three exons/ two introns organization of the CC chemokine family. 12 Upon sequencing of the entire RANTES gene, seven single nucleotide polymorphisms (SNPs) were identifi...

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Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with histological activity of liver disease

Cited by 56 publications

References 0 publications

CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis

Haplotype-taggingRANTES gene variants influence response to antiviral therapy in chronic hepatitis C

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