CXCL9 and CXCL10 Chemokines as Predictors of Liver Fibrosis in a Cohort of Primarily African-American Injection Drug Users With Chronic Hepatitis C

Zeremski, Marija; Dimova, Rositsa B.; Astemborski, Jacquie; Thomas, David L.; Talal, Andrew H.

doi:10.1093/infdis/jir424

Cited by 49 publications

(55 citation statements)

References 13 publications

(21 reference statements)

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“…CXCR3 ligands have been extensively investigated in animal studies [6,10,13,15,23,34], as well as in humans with liver disease [5,9,11,12,16,18,26,27,35]. Different studies have assessed a relationship between CXCR3 ligands and fibrosis and hepatic injury [8][9][10][12][13][14][15][16][17][18], angiogenesis [6], and complications of liver cirrhosis [19].…”

Section: Discussionmentioning

confidence: 99%

“…These processes themselves are at least partly initiated and modulated by chemokines [3,4]. In particular, CXCR3 ligands, especially CXCL9, are increased during liver diseases [5][6][7][8][9][10][11][12] and are functionally linked to hepatic injury, inflammation, fibrosis, [8][9][10][12][13][14][15][16][17][18], angiogenesis [6] and complications of cirrhosis [19]. Liver resident cells, such as hepatocytes, Kupffer cells and hepatic stellate cells were found to represent a major source of CXCR3 ligands in the liver [20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

“…Liver resident cells, such as hepatocytes, Kupffer cells and hepatic stellate cells were found to represent a major source of CXCR3 ligands in the liver [20][21][22][23][24][25]. The increased intrahepatic levels of CXCR3 ligands during liver disease are also paralleled by elevated serum levels, as demonstrated in various animal and human studies [8,11,13,14,[16][17][18][19][26][27][28]. Circulating inflammatory cells, in addition to liver resident cells, might contribute to their synthesis and secretion as shown previously [23,29].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Berres¹,

Asmacher²,

Lehmann³

et al. 2015

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Berres¹,

Asmacher²,

Lehmann³

et al. 2015

Journal of Hepatology

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“…High levels of IP-10 levels are known to be associated with reduced rates of sustained virological response during treatment of HCV with pegylated (PEG)-IFN/ribavirin (RBV) [37,[47][48][49] HIV-1/HCV coinfection [38,50] and reduced spontaneous clearance to acute infection [51]. Further, high IP-10 levels have been associated with greater inflammation and liver fibrosis [48,49] even in a cohort of African-American injection drug users with chronic HCV [52]. Thus, these increased levels of IP-10 within the HIV-1/HCV co-infected individuals in the CARES Cohort could likely be a marker of reduced response to therapy, immunologic dysfunction ultimately leading to an accelerated progression of disease.…”

Section: Discussionmentioning

confidence: 99%

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

Wigdahl¹

2016

MOJI

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Submit Manuscript | http://medcraveonline.com infection that is spontaneously cleared [3].However, in cases of HIV-1 and HCV coinfection, the number of chronic HCV infections rises to 90% [4]. The result of any viral infection depends on the interplay between the activation of host cellular factors to the infection and the viral mechanisms that counteract them [5]. HCV is responsible for activating antiviral interferon (IFN)-α/β expression, but irrespective of the expression of these cytokines, HCV can still replicate within the liver [6]. This could be due to the fact that the nonstructural proteins, nonstructural protein (NS)3 and NS5A, and the structural protein E2 can block the expression as well as transcription of IFN-α/β genes. Also, the NS5A protein induces expression of interleukin (IL)-8, associated with IFN-α inhibition [7] HCV can also block the antiviral action of natural killer (NK) and NKT cells thus hindering the expression of IFN-γ (an antiviral cytokine) due to the interaction between E2 and NK-cell CD81 molecule [8]. The production of cytokines by dendritic cells (DCs) is particularly affected by chronic HCV infection and there are contradictory reports concerning the expression of Th1 cytokines, with some studies suggesting that a Th1 response is suppressed [9] and some studies suggesting a progressive liver injury during chronic HCV has been associated with an increase in the Th1 responseassociated cytokines [10]. In this regard, HCV CD4 + T cells also play an important role in providing an adaptive response by activating cytotoxic and humoral responses. This can involve the secretion AbstractHIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Thus, coinfection with HIV-1 and HBV or HCV is common. HIV-1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward endstage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 has also been associated with increased mortality when compared to either infection alone. In particular, we focus on the impact of coinfection with HCV on the HIV-1 pathogenic process in patients in the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Comparing HIV-1 mono-infection with HIV-1/HCV coinfection allows defining the detrimental effect of HCV coinfection as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay, in the background of drug abuse, which is an important risk factor to both HIV-1 and HCV infection and on HIV-1 disease severity. The uniqueness of this study includes the fact that the patients are part of a cohort of HIV-1-infected individuals whose drug histories have been recorded longitudinally.

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“…Clinical studies have been showed that the levels of the IFN-γ inducible chemokines CXCL9-11 are significantly up-regulated in the serum and livers of patients with various liver disease [1,[12][13][14]. The high levels of CXCL9-11 have been found to be independently related to the development of clinically hepatic disease [15,16]. According to some studies, elevated serum and intrahepatic CXCL9 and CXCL10 expression levels have been reported as important prognostic and predictive biomarkers of progressive liver injury [17][18][19][20], CXCL11, which is also expressed by hepatocytes, involves in pro-inflammatory T cells recruitment and differentiation [7].…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Interferon-γ-Inducible Genes Expression in Hepatocytes through Down-Regulating Activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK and PI3K/Akt Signaling Pathways

Wu¹,

Xue²,

Yang³

et al. 2015

Cell Physiol Biochem

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Background & Aims: The high expression levels of interferon-γ (IFN-γ)-inducible genes correlate positively with liver diseases. The present study aimed to explore the effect of isoliquiritigenin (ISL) on the expression of genes induced by IFN-γ in vitro, and to elucidate the underlying molecular mechanisms. Methods: HepG2 and L02 cells were divided into control, ISL, IFN-γ, and IFN-γ plus ISL groups. The cytotoxicity of compounds to cells was evaluated by Cell Counting Kit 8 (CCK8) assay; the expression levels of chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, CXCL11, and interleukin-6 (IL-6) in cells and supernatant were measured by quantitative real time polymerase chain reaction (qRT-PCR) and ELISA, respectively. Moreover, western blot was used to examine the phosphorylated levels of janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1), nuclear factor (NF)-γB, interferon regulatory factor 3 (IRF3)/myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (Akt) in HepG2 and L02 cells exposed to ISL, IFN-γ and IFN-γ plus ISL. Results: The results showed that IFN-γ treatment induced the expression of CXCL9, CXCL10, CXCL11, and IL-6 in HepG2 and LO2 cells, which could be significantly and dose-dependently inhibited by ISL treatment (P < 0.05 or P < 0.01), but the inhibitory effect of ISL on IL-6 expression was not so good as on CXCL9, CXCL10, and CXCL11 expression. Furthermore, ISL treatment dose-dependently inhibited the activation of JAK1/STAT1, IRF3/MyD88, extracellular signal-regulated kinase (ERK)/MAPK, c-Jun N-terminal kinase (JNK)/MAPK, and PI3K/Akt signaling pathways (P < 0.05), but had no effect on the activation of JAK2/STAT1, NF-γB and p38/MAPK signaling pathways. Conclusion: We demonstrate that ISL inhibits IFN-γ-induced inflammation in hepatocytes via influencing the activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK, and PI3K/Akt signaling pathways.

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CXCL9 and CXCL10 Chemokines as Predictors of Liver Fibrosis in a Cohort of Primarily African-American Injection Drug Users With Chronic Hepatitis C

Cited by 49 publications

References 13 publications

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

Isoliquiritigenin Inhibits Interferon-γ-Inducible Genes Expression in Hepatocytes through Down-Regulating Activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK and PI3K/Akt Signaling Pathways

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