UNIPROT:P10145 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines and chemokines are proteins that play a critical role in the regulation of immunity and inflammation in patients with chronic Hepatitis C. The aim of our study was to correlate serum cytokines, chemokines and apoptosis in non-treated chronic hepatitis C patients with various degrees of inflammation and fibrosis. We studied 778 patients: 59 had low Knodell fibrosis score and low Knodell histological activity index; 372 had mild fibrosis and low histological activity index; 270 had moderate fibrosis and moderate histological activity index; and, 77 had high fibrosis and high histological activity index on their biopsy. Serum cytokines, chemokines and apoptosis were measured by enzyme-linked-immunosorbent-assay. Multivariate analysis was employed for statistical purposes. A positive correlation was seen between the degree of inflammation and tumor necrosis factor-alpha (TNF-alpha) levels (r = 0.92) in non-cirrhotic patients and between interleukin 2 in all patients (r = 0.85). Interleukin-8 increased significantly at higher histological activity indices and continued to increase in patients with cirrhosis. Transforming growth factor-beta (TGF-beta) levels increased significantly with the severity of fibrosis, but decreased in cirrhotics. In conclusion, cytokines, chemokines and apoptosis levels reflect the progression of inflammation and fibrosis in hepatitis C infected patients, but their signatures differ.
...
PMID:Cytokine--chemokine and apoptotic signatures in patients with hepatitis C. 1732 Jul 98

Hepatitis C virus (HCV) Core has been implicated in immune-mediated mechanisms associated with the development of chronic hepatic diseases. Discovery of different alternative reading frame proteins (ARFPs) expressed from the HCV Core coding sequence challenges properties assigned to Core. This study was designed to evaluate the immunomodulatory functions of Core and ARFPs in monocytes, dendritic cells (DCs), macrophages (Mphi) and hepatocytes, cells that are all capable of supporting HCV replication. THP-1 cells, monocyte-derived Mphi and DCs, and Huh7 cells were infected by using adenoviruses (Ad) encoding Core, CE1E2 and a Core sequence modified so that the Core protein is wild type, but no ARFPs are expressed (CDeltaARFP). THP-1 cells and DCs infected with Ad encoding Core or CE1E2 produced significant levels of interleukin-6 (IL-6), IL-8, MCP-1 and MIP-1beta, whereas production of these chemokines with AdCDeltaARFP was reduced or abolished. Similar effects on IL-8 production were observed in Huh7 cells and on IL-6 and MIP-1beta in Mphi. Wild-type Core sequence, but not CDeltaARFP, could trans-activate the IL-8 promoter and this activation was not associated with activation of p38/p42-44MAPK. This study illustrates, for the first time, the critical importance of ARFP expression in immunomodulatory functions attributed to Core expression and suggests a potential involvement of ARFP in mechanisms associated with HCV pathogenesis.
...
PMID:Expression of the alternative reading frame protein of Hepatitis C virus induces cytokines involved in hepatic injuries. 1737 58

HIV-1 infection is associated with dysregulation of cytokine production by peripheral blood (PB) monocytes and dendritic cells (DC), but controversial results have been reported. We aimed to analyze the effect of antiretroviral therapy (ART) on the in vitro production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin -CD33(high+ ) myeloid DC (mDC) and CD33(+)/CD14(-/dim+)/CD16(high+) DC- from HIV-1+ patients and its relationship with CD4+ T-cell recovery and co-infection with hepatitis C virus (HCV). In vitro cytokine production was analyzed at the single cell level in 32 HIV-1+ patients, grouped according to the number of CD4+ T-cells/microl in PB (<200 CD4 versus >200 CD4). Patients were tested prior to therapy and at weeks +2, +4, +8, +12 and +52 after ART. Prior to ART, production of IL-6, TNF-alpha and IL-12 by mDC and of IL-8 and IL-12 by CD16+ DC was significantly increased among >200 CD4 patients. After one year of ART, increased production of IL-8 by monocytes, of TNF-alpha by mDC and of IL-1beta, IL-6 and TNF-alpha by CD16+ DC was specifically observed among <200 CD4 HIV-1+ individuals showing a high recovery of PB CD4+ T-cell counts. In turn, we found that the significantly reduced percentage of IL-1beta, IL-6, IL-8 and TNF-alpha-producing monocytes and of IL-6 and IL-8-producing mDC and CD16+ DC, as well as the significantly diminished mean amount of IL-6 produced per monocyte, mDC and CD16+ DC and of IL-12 produced per CD16+ DC observed at week +52 for the >200 CD4 patients, were related to the presence of co-infection with HCV. In summary, HIV-1+ individuals show abnormal production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin even after one year of ART, such abnormalities being associated with the degree of recovery of PB CD4+ T-cell counts in more immunocompromised patients and HCV co-infection in more immunocompetent HIV-1+ individuals.
...
PMID:Abnormal cytokine production by circulating monocytes and dendritic cells of myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and HCV co-infection. 1750 74

Recent studies have indicated that cytokines can be used as markers for disease progression in hepatitis C virus (HCV)-infected patients, therefore this study was conducted to determine the influence of pegylated IFN vs standard IFN on interleukin-2 receptor (IL-2R), IL-6R, IL-8, TNFR-I, TNFR-II, sFas, and sFas-L in Egyptian patients with chronic hepatitis C genotype 4, as no previous studies have been performed on this genotype. We also aim at establishing a possible relationship between these cytokines and the response to INF to determine whether they can be used as noninvasive markers for the response to INF therapy and as monitors for the outcome of treatment. Thirty-eight patients with chronic HCV hepatitis were investigated for the serum levels of the previously mentioned cytokines in a randomized opened controlled trial (22 patients treated with pegylated IFN and 16 patients treated with standard IFN). Cytokine levels were measured by ELISA at 0, 1 and 12 months of IFN therapy. There was marked increase in the serum levels of IL-2R and IL-6R in nonresponders to pegylated interferon, IL-8, TNFR-I and II were significantly higher in nonresponders to standard interferon but were also high in responders of pegylated interferon. sFas and sFas-L showed high levels among responders to pegylated interferon but the standard interferon was again less effective in this regard. Serum levels of TNFR-II, sFas and sFas-L have the potential to be used as serological markers for response to pegylated IFN therapy, and IL-8 is a predictor for nonresponse. Moreover, TNFR-I and II have the potential to be used as markers of response to standard IFN treatment. The persistent correlation between sFas and TNFR-II may elaborate the possible role of pegylated IFN in the induction of apoptosis as a possible new mechanism of viral clearance during treatment with pegylated interferon treatment.
...
PMID:Immunomodulators, sFas and Fas-L as potential noninvasive predictors of IFN treatment in patients with HCV genotype-4. 1757 88

Hepatitis C is a devastating disease worldwide. Proteins encoded by the etiologic agent, hepatitis C virus (HCV), are believed to play important roles in HCV-associated pathogenesis. However, the biological functions of the non-structural protein-2 (NS2) encoded by HCV are not well characterized. Here, we show that HCV NS2 protein activates CXCL-8 (interleukin-8, IL-8) transcription in HepG2 cells as measured by reverse transcription-polymerase chain reaction and IL-8 promoter-luciferase reporter assays. Furthermore, when the kappaB site on the IL-8 promoter was eliminated by mutagenesis or when intracellular NF-kappaB activity was suppressed by an inhibitor, NS2 did not activate the IL-8 promoter, suggesting a role of NF-kappaB in this process. These results prompted us to hypothesize that HCV NS2 might be able to activate NF-kappaB. This hypothesis was tested by determination of NF-kappaB-driven reporter gene expression and NF-kappaB p65 subunit subcellular localization after HCV NS2 expression. Indeed, NS2 could up-regulate NF-kappaB-driven luciferase activity and was associated with p65 nuclear localization. These results demonstrate that HCV NS2 up-regulates IL-8 transcription through NF-kappaB. This newly identified function increases our understanding of the role of HCV NS2 protein in virus-host interactions.
...
PMID:Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through NF-kappaB. 1807 95

The hepatitis C virus (HCV) non-structural (NS) 3/4A protein complex inhibits the retinoic acid inducible gene I (RIG-I) pathway by proteolytically cleaving mitochondria-associated CARD-containing adaptor protein Cardif, and this leads to reduced production of beta interferon (IFN-beta). This study examined the expression of CCL5 (regulated upon activation, normal T-cell expressed and secreted, or RANTES), CXCL8 (interleukin 8) and CXCL10 (IFN-gamma-activated protein 10, or IP-10) chemokine genes in osteosarcoma cell lines that inducibly expressed NS3/4A, NS4B, core-E1-E2-p7 and the entire HCV polyprotein. Sendai virus (SeV)-induced production of IFN-beta, CCL5, CXCL8 and CXCL10 was downregulated by the NS3/4A protein complex and by the full-length HCV polyprotein. Expression of NS3/4A and the HCV polyprotein reduced the binding of interferon regulatory factors (IRFs) 1 and 3 and, to a lesser extent, nuclear factor (NF)-kappaB (p65/p50) to their respective binding elements on the CXCL10 promoter during SeV infection. Furthermore, binding of IRF1 and IRF3 to the interferon-stimulated response element-like element, and of c-Jun and phosphorylated c-Jun to the activator protein 1 element of the CXCL8 promoter, was reduced when NS3/4A and the HCV polyprotein were expressed. In cell lines expressing NS3/4A and the HCV polyprotein, the subcellular localization of mitochondria was changed, and this was kinetically associated with the partial degradation of endogenous Cardif. These results indicate that NS3/4A alone or as part of the HCV polyprotein disturbs the expression of IRF1- and IRF3-regulated genes, as well as affecting mitogen-activated protein kinase kinase- and NF-kappaB-regulated genes.
...
PMID:Hepatitis C virus proteins interfere with the activation of chemokine gene promoters and downregulate chemokine gene expression. 1819 74

A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-beta)), and IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-alpha (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-beta (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-alpha, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-alpha was significantly related to albumin and prothrombin activity, whereas TGF-beta was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-beta.
...
PMID:Cytokines and lipid peroxidation in alcoholics with chronic hepatitis C virus infection. 1821 80

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen-activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF-alpha inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti-inflammatory peroxisome proliferator-activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV-associated IR and provides a direction for future research in the areas of therapeutic intervention.
...
PMID:Hepatitis C virus infection: molecular pathways to metabolic syndrome. 1875 83

Characterization of the immune responses induced in the initial stages of human immunodeficiency virus type 1 (HIV-1) infection is of critical importance for an understanding of early viral pathogenesis and prophylactic vaccine design. Here, we used sequential plasma samples collected during the eclipse and exponential viral expansion phases from subjects acquiring HIV-1 (or, for comparison, hepatitis B virus [HBV]or hepatitis C virus [HCV]) to determine the nature and kinetics of the earliest systemic elevations in cytokine and chemokine levels in each infection. Plasma viremia was quantitated over time, and levels of 30 cytokines and chemokines were measured using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. The increase in plasma viremia in acute HIV-1 infection was found to be associated with elevations in plasma levels of multiple cytokines and chemokines, including rapid and transient elevations in alpha interferon (IFN-alpha) and interleukin-15 (IL-15) levels; a large increase in inducible protein 10 (IP-10) levels; rapid and more-sustained increases in tumor necrosis factor alpha and monocyte chemotactic protein 1 levels; more slowly initiated elevations in levels of additional proinflammatory factors including IL-6, IL-8, IL-18, and IFN-gamma; and a late-peaking increase in levels of the immunoregulatory cytokine IL-10. Notably, there was comparatively little perturbation in plasma cytokine levels during the same phase of HBV infection and a delayed response of more intermediate magnitude in acute HCV infection, indicating that the rapid activation of a striking systemic cytokine cascade is not a prerequisite for viral clearance (which occurs in a majority of HBV-infected individuals). The intense early cytokine storm in acute HIV-1 infection may have immunopathological consequences, promoting immune activation, viral replication, and CD4(+) T-cell loss.
...
PMID:Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. 1917 32

The Hepatitis C virus nonstructural 5A (NS5A) protein is a hydrophilic phosphoprotein with diverse functions. The domain assignment of NS5A had been refined using a systematic in silico bioinformatics approach using DOMAC, the protein is divided into three domains and domain III is subdivided into two subdomains using ProDom and SSEP servers. The fold structure for domains II and III were predicted using the meta-server 3D-Jury. Scanning motif databases (SMART, BLOCKS, and PROSITE) gave new motifs. Two important motifs, the interleukins 1 and 8 interaction motifs, relating to NS5A function in inducing the interleukin 8 promoter, were discovered from the BLOCKS scan. Protein-protein interaction motifs were predicted as hot loops and disordered regions, corresponding to binding regions with the ds-protein kinase R, viral polymerase, and Src homology 3 signaling proteins binding motif. Other hot loops were predicted in the V3 region and in the single-stranded DNA-binding protein motif. The different mechanisms by which the NS5A protein leads to immune system signaling dysfunction points to the natural genetic engineering of this protein.
...
PMID:Natural genetic engineering of hepatitis C virus NS5A for immune system counterattack. 1984 37

<< Previous 1 2 3 4 5 6 7 Next >>