Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While the impact of the dengue viruses on liver function is prominent as shown by hepatomegaly, liver enzyme abnormality, occasional fulminant hepatic failure and histological changes including hepatocellular necrosis, significant debate exists as to the possible involvement of the predominant cell type in the liver, hepatocytes, in the disease process. To address this issue purified human primary hepatocytes were exposed to dengue virus serotype 2 and the production of de novo viral progeny was established by standard plaque assay, RT-PCR and immunocytochemistry. To investigate the response of the primary hepatocytes to infection, the expression of a panel of 9 cytokine genes (IFN-beta, TRAIL, MCP-1, IL-6, IL-1beta, IL-8, MIP-1alpha, MIP-1beta, and RANTES) was semi-quantitatively investigated by RT-PCR and up-regulation of TRAIL, MIP-1alpha, IFN-beta, MIP-1beta, IL-8, and RANTES was observed in response to infection. The induction of IL-8 in response to infection was accompanied by the secretion of IL-8 as verified by ELISA assay. The ability of hepatocytes to be infected with dengue virus serotype 2 in vitro support evidence implicating human hepatocytes as a target cell in cases of dengue virus infection, and provide the first experimental evidence to support the large number of clinical studies that implicate the liver as a critical target organ in severe cases of dengue infection.
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PMID:Infection of human primary hepatocytes with dengue virus serotype 2. 1724 28

A microarray for demonstration of a limited number of porcine cytokines was initiated. Polymerase chain reaction (PCR) products were synthesized for four house-keeping genes, cyclophilin, beta-actin, hypoxanthine phosphoribosyltransferase (HPRT) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, IL-18, interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumour necrosis factor (TNF)-alpha, macrophage inhibition factor (MIF) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Cytokine production was induced by incubation of porcine peripheral blood mononuclear cells (PBMC) with Concanavalin A (ConA) or oligodeoxynucleotide (ODN) 2216. RNA was isolated after 6 or 24 h from stimulated cells or unstimulated control cells and from intestinal biopsies. Cytokine expression was analysed using a 3-DNA Array 350(TM) labelling kit from Genisphere. Data were normalized using external control genes and analysed with the genepix pro 5.0 software. All the cytokines could be induced in PBMC and expressed on the array and the cytokines IL-6 and IFN-alpha were also analysed at protein level. All but one cytokine were expressed in samples from intestinal biopsies. Densitometric analyses of PCR products of the house-keeping genes were performed to validate the results from the microarray. Thus, this microarray will enable analyses of the cytokine profile during local and systemic infections in the pig.
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PMID:Development of a microarray for studying porcine cytokine production in blood mononuclear cells and intestinal biopsies. 1738 82

Fibrinogen, in addition to its role in coagulation, is also an acute phase protein of inflammation. Treatment of adherent human monocytes with fibrinogen increases IL-8, IL-6, and TNF-alpha, but has no effect on MCP-1, IFN-beta, or IP-10. Treatment of monocytes with fibrinogen and C5a doubles IL-8 and IL-6 production, compared to fibrinogen alone. The increase in cytokine production was accompanied by a transient increase in IL-8 mRNA and increased NF-kappaB activity. Monocytes from an IRAK-4- and two NEMO-deficient patients had 80% reduced IL-8 responses to fibrinogen. Moreover, responses to fibrinogen were blocked with anti-CD14 antibody (MY4), a subunit of the LPS receptor. The data indicate that fibrinogen alone and fibrinogen plus C5a are potent inducers of cytokine production in monocytes, and that signaling by fibrinogen is mediated through the TLR-4 pathway.
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PMID:Induction of human monocyte interleukin (IL)-8 by fibrinogen through the toll-like receptor pathway. 1762 83

Pancreatic carcinoma is one of the most lethal of the gastrointestinal malignant tumors. Chronic inflammation leads to cancer development and progression. Interleukin-8 (CXCL-8) is a CXC chemokine, which plays an important role in neutrophil chemotaxis and activation. We previously reported that CXCL-8 was produced by a variety of human carcinoma cells and tissues, and that CXCL-8 promoted proliferation in pancreatic carcinoma cells (SUIT-2). In the present study, we analyzed whether various cytokines affect cell proliferation by CXCL-8 expression in pancreas carcinoma cells. All examined pancreatic carcinoma cells expressed CXCL-8 and TNFRII mRNA constitutively in RPMI-1640 medium without FBS. TNF-alpha, LIF, IL-1beta, IL-6, IL-8, or IFN-beta enhanced the expression of CXCL-8 mRNA, but IL-10 did not in Hs-700T cells. Actinomycin D suppressed and cycloheximide augmented CXCL-8 mRNA which was induced by TNF-alpha or not. The half-life of CXCL-8 mRNA was 36.5 min by TNF-alpha and 35.2 min by no stimulation. In our previous study, LIF promoted cell growth in Hs-700T cells. LIF induced CXCL-8 mRNA in a dose- and time-dependent manner. Addition of recombinant CXCL-8 did not induce cell growth of Hs-700T. Anti-CXCL-8 IgG significantly suppressed cell growth. CXCL-8 would act as an autocrine growth factor in Hs-700T cells, which expressed CXCL-8 mRNA highly without stimulation. Curcumin (diferuloylmethane), NF-kappaB inhibitor, suppressed cell proliferation in Hs-700T cells. These results suggest that CXCL-8 plays a pivotal role in progression of pancreatic cancer, and its expression is influenced by inflammatory cytokines in pancreatic tumor microenvironment.
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PMID:Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor. 1767 91

Type I IFNs are used for treating viral, neoplastic, and inflammatory disorders. The protein products encoded by IFN-stimulated genes (ISGs) likely mediate clinical effects of IFN in patients. Macroarray assays, used for studying ISG induction in IFN-treated patients, comprise genes identified predominantly through analysis of long-term cell lines. To discover genes induced selectively by IFN-beta in PBMC, we exposed whole blood to physiological concentrations of IFN-beta. PBMC were prepared, and RNA was extracted, reverse-transcribed, and hybridized to cDNA microarrays, and microarray analysis identified 39 ISGs and 20 IFN-repressed genes (IRGs). Thirty-three ISGs were known previously, and six ISGs were novel. New ISGs included GTP cyclohydrolase 1; hypothetical protein LOC129607; hypothetical protein FLJ38348; leucine aminopeptidase 3; squalene epoxidase; and GTP-binding protein overexpressed in skeletal muscle. Twenty IRGs included IL-1beta and CXCL8, which had been identified earlier. CXCL1 was a novel IRG identified in the current study. PCR analysis demonstrated the regulation of six novel ISGs and CXCL1 as an IRG in PBMC and astrocytoma cells. Results were validated using RNA obtained ex vivo from blood of patients after injection with IFN-beta. Identification of new ISGs and IRGs in primary PBMC will enhance macroarray assays for monitoring IFN responsiveness.
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PMID:Novel interferon-beta-induced gene expression in peripheral blood cells. 1770

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.
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PMID:Hepatitis C virus proteins interfere with the activation of chemokine gene promoters and downregulate chemokine gene expression. 1819 74

Human HepaRG cells are liver progenitors which possess hepatocyte-like functionality. We investigated the effects of double-stranded (ds) RNA on interferon (IFN)-beta and chemokine (CK) expression in these cells. By microarray and ELISA, we showed strong induction of CXCL10 and interleulin (IL)-8 besides IFN-beta and other CK ligands. RNA interference directed silencing of TLR3, RIG-I, IRF3, NFkappaB or MAP kinases (p38, ERK, JNK) was carried out. Knockdown of all these molecules, except ERK and JNK, blocked IFN-beta production. Both TLR3 and RIG-I are required for CXCL10 expression. Silencing of TLR3 completely impaired the IL-8 expression. dsRNA-conditioned medium from HepaRG cells exerted a drastic antiviral effect in HCV replicons, and in the JFH-1-based HCV production cell culture system. The IFN-beta knockdown in HepaRG cells removed this antiviral effect but did not enhance their capacity to initiate HCV RNA replication. We conclude that dsRNA induces antiviral and pro-inflammatory status in HepaRG cells.
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PMID:Characterization of the double-stranded RNA responses in human liver progenitor cells. 1825 84

Neutrophils, historically known for their involvement in acute inflammation, are also targets for infection by many different DNA and RNA viruses. However, the mechanisms by which they recognize and respond to viral components are poorly understood. Polyinosinic:polycytidylic acid (poly(I:C)) is a synthetic mimetic of viral dsRNA that is known to interact either with endosomal TLR3 (not expressed by human neutrophils) or with cytoplasmic RNA helicases such as melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I). In this study, we report that intracellularly administered poly(I:C) stimulates human neutrophils to specifically express elevated mRNA levels encoding type I IFNs, immunoregulatory cytokines, and chemokines, such as TNF-alpha, IL-12p40, CXCL10, CXCL8, CCL4, and CCL20, as well as classical IFN-responsive genes (IRG), including IFIT1 (IFN-induced protein with tetratricopeptide repeats 1)/IFN-stimulated gene (ISG)56, G1P2/ISG15, PKR (dsRNA-dependent protein kinase), and IFN-regulatory factor (IRF)7. Investigations into the mechanisms whereby transfected poly(I:C) promotes gene expression in neutrophils uncovered a crucial involvement of the MAPK-, PKR-, NF-kappaB-, and TANK (TNF receptor-associated NF-kappaB kinase)-binding kinase (TBK1)/IRF3-signaling transduction pathways, as illustrated by the use of specific pharmacological inhibitors. Consistent with the requirement of the cytoplasmic dsRNA pathway for antiviral signaling, human neutrophils were found to constitutively express significant levels of both MDA5 and RIG-I, but not TLR3. Accordingly, neutrophils isolated from MDA5-deficient mice had a partial impairment in the production of IFN-beta and TNF-alpha upon infection with encephalomyocarditis virus. Taken together, our data demonstrate that neutrophils are able to activate antiviral responses via helicase recognition, thus acting at the frontline of immunity against viruses.
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PMID:Activation of an immunoregulatory and antiviral gene expression program in poly(I:C)-transfected human neutrophils. 1894 Dec 47

Alveolar type II epithelial cells (ATIIs) are one of the primary targets for influenza A pneumonia. The lack of a culture system for maintaining differentiated ATIIs hinders our understanding of pulmonary innate immunity during viral infection. We studied influenza A virus (IAV)-induced innate immune responses in differentiated primary human ATIIs and alveolar macrophages (AMs). Our results indicate that ATIIs, but not AMs, support productive IAV infection. Viral infection elicited strong inflammatory chemokine and cytokine responses in ATIIs, including secretion of IL-8, IL-6, MCP-1, RANTES, and MIP-1beta, but not TNF-alpha, whereas AMs secreted TNF-alpha as well as other cytokines in response to infection. Wild-type virus A/PR/8/34 induced a greater cytokine response than reassortant PR/8 virus, A/Phil/82, despite similar levels of replication. IAV infection increased mRNA expression of IFN genes IFN-beta, IL-29 (IFN-lambda1), and IL-28A (IFN-lambda2). The major IFN protein secreted by type II cells was IL-29 and ATIIs appear to be a major resource for production of IL-29. Administration of IL-29 and IFN-beta before infection significantly reduced the release of infectious viral particles and CXC and CC chemokines. IL-29 treatment of type II cells induced mRNA expression of antiviral genes MX1, OAS, and ISG56 but not IFN-beta. IL-29 induced a dose-dependent decrease of viral nucleoprotein and an increase of antiviral genes but not IFN-beta. These results suggest that IL-29 exerts IFN-beta-independent protection in type II cells through direct activation of antiviral genes during IAV infection.
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PMID:Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. 1915 75

Human rhinoviruses (HRV) are a major cause of asthma exacerbations and hospitalization. Studies using primary cultures suggest that this may be due to impaired production of type I and type III IFNs by asthmatic bronchial epithelial cells. Although epithelial cells are the main target for HRV infection, HRV can be detected in the subepithelial layer of bronchial mucosa from infected subjects by in situ hybridization. Therefore, we postulated that submucosal fibroblasts are also involved in the innate antiviral response to HRV infection in asthma. We found that regardless of subject group, bronchial fibroblasts were highly susceptible to RV1b infection. IL-8 and IL-6 were rapidly induced by either HRV or UV-irradiated virus, suggesting that these responses did not require viral replication. In contrast, RANTES expression was dependent on viral replication. Regardless of disease status, fibroblasts did not respond to HRV infection with significant induction of IFN-beta, even though both groups responded to synthetic dsRNA with similar levels of IFN-beta expression. Exogenous IFN-beta was highly protective against viral replication. Our data suggest that fibroblasts respond to HRV with a vigorous proinflammatory response but minimal IFN-beta expression. Their susceptibility to infection may cause them to be a reservoir for HRV replication in the lower airways, especially in asthmatic subjects where there is reduced protection offered by epithelial-derived IFNs. Their ability to support viral replication coupled with their vigorous proinflammatory response following infection may contribute to asthma exacerbations.
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PMID:Contribution of bronchial fibroblasts to the antiviral response in asthma. 1926 44


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