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)

Influenza virus-induced epithelial damage may be mediated, in part, by reactive oxygen intermediates (ROIs). In this study, we investigated the role of ROIs in the influenza virus-induced gene expression of antioxidant enzymes and in the activation of nuclear factor-kappa B (NF-kappa B), an oxidant-sensitive transcriptional factor. Influenza virus infection increased production of intracellular ROIs in A549 pulmonary epithelial cells. Induction of manganese superoxide dismutase (MnSOD) mRNA correlated with increased MnSOD protein and enzyme activity. Influenza virus infection also activated NF-kappa B binding as determined by an electrophoretic mobility shift assay. Pretreatment of A549 cells with N-acetyl-L-cysteine attenuated virus-induced NF-kappa B activation and interleukin (IL)-8 mRNA induction but did not block induction of MnSOD mRNA. In contrast, pyrrolidine dithiocarbamate blocked activation of NF-kappa B and induction of MnSOD and IL-8 mRNAs. Treatment with pyrrolidine dithiocarbamate also markedly decreased virus-induced cell death. Thus oxidants are involved in influenza virus-induced activation of NF-kappa B, in the expression of IL-8 and MnSOD, and in virus-induced cell death.
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PMID:Role of oxidants in influenza virus-induced gene expression. 945 11

Upper respiratory viruses cause self-limited illness characterized by acute rhinitis. In rhinovirus colds the symptoms are thought to be caused by the host response rather than viral damage of the nasal epithelium. Rhinovirus triggers an inflammatory cascade, evidenced by the presence of inflammatory mediators (e.g., IL-8) and proinflammatory cytokines (e.g., kinins) in nasal secretions, which results in symptomatic illness. In contrast to rhinovirus and coronavirus, which do not cause discernible epithelial damage, influenza virus and adenovirus do damage the nasal epithelium. Appropriate antiviral therapy will depend on the causative virus. Treatment of rhinovirus colds may require an antiviral agent (e.g., interferon alpha) in combination with antiinflammatory medication.
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PMID:Viral-induced rhinitis. 951 54

After influenza A virus infection of human monocytes, we found a rapid and marked release of the mononuclear cell attracting chemokines MCP-1, MIP-1 alpha, and IP-10, with corresponding gene expression patterns as determined by Northern blot analysis. In striking contrast, the expression and release of the neutrophil chemoattractant IL-8 was not inducible. To determine the underlying mechanisms responsible for the induction of this differential chemokine pattern, we stimulated monocytes with UV- and heat-inactivated (56 degrees C and 100 degrees C) influenza A virus. In comparison with fully infectious influenza A, 56 degrees C-inactivated virus induced a strong production of MCP-1, MIP-1 alpha, and IP-10, while the release of MIP-1 alpha and IP-10 was substantially lower after exposure to UV-inactivated virus. No chemokine expression was found after stimulation with 100 degrees C-inactivated influenza A virus. Our data indicate that, contingent upon the chemokine examined, the maximal induction depends on the unrestricted infectivity of the virus, the unaltered hemagglutinin molecule, or the intact viral RNA. This diversified chemokine production may enable the infected host to mount an efficient antiviral response against infective and noninfective virus particles.
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PMID:Differential mononuclear leukocyte attracting chemokine production after stimulation with active and inactivated influenza A virus. 963 59

The roles of interleukin (IL)-6 and IL-8 in mediating the symptoms and signs of influenza A infection were examined. Adults were intranasally inoculated with a rimantadine-sensitive strain of influenza A HlNl virus and treated with rimantadine or placebo. Viral shedding, secretion weights, symptom scores, and concentrations of IL-6 and IL-8 in nasal lavage fluids were compared between treatment groups. Viral shedding was associated with increases in local and systemic symptoms, in expelled secretion weights, and in levels of IL-6 and IL-8. Compared with placebo, rimantadine treatment reduced viral shedding, systemic symptoms, and levels of IL-8. Days of viral shedding and IL-6 but not IL-8 concentrations were significantly correlated with the other measures of symptoms and signs. These data support a causal relationship between viral replication, cytokine production, and symptom expression, and they suggest that IL-6 may have a role in mediating symptom and sign expression during influenza A infection.
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PMID:Evidence for cytokine mediation of disease expression in adults experimentally infected with influenza A virus. 1035 55

Airway epithelial cells which are the initial site of influenza virus (IV) infection are suggested to participate in airway inflammatory response by expressing various cytokines including RANTES; however, the intracellular signal that regulates RANTES expression has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase, extracellular signal-regulated kinase (Erk), and c-Jun-NH2-terminal kinase (JNK) in RANTES production by IV-infected human bronchial epithelial cells. The results showed that IV infection induced increases in p38 MAP kinase, and Erk and JNK phosphorylation and activity. SB 203580, PD 98059, and CEP-1347 attenuated IV-infection induced p38 MAP kinase activity, Erk activity, and JNK activity, respectively. SB 203580 and CEP-1347 attenuated RANTES production by 45.3% and 45.2%, respectively, but a combination of these inhibitors additively attenuated by 69.1%. In contrast, PD 98059 did not attenuate. Anti-IL-1alpha mAb, anti-IL-1beta mAb, anti-TNF-alpha mAb, anti-IL-8 mAb, anti-IFN-beta mAb, anti-RANTES mAb, and a combination of these mAbs did not affect IV infection-induced increases in p38 MAP kinase, Erk, and JNK phosphorylation, indicating that each cytokine neutralized by corresponding Ab was not involved in IV infection-induced phosphorylation of MAP kinases. N-acetylcysteine (NAC) did not affect IV infection-induced increases in MAP kinase phosphorylation, whereas NAC attenuated RANTES production by 18.2%, indicating that reactive oxygen species may act as a second messenger leading to RANTES production via p38 MAP kinase- and JNK-independent pathway. These results indicate that p38 MAP kinase and JNK, at least in part, regulate RANTES production by bronchial epithelial cells.
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PMID:p38 mitogen-activated protein kinase and c-jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. 1070 14

Chemokines regulate leukocyte traffic and extravasation into the site of inflammation. Here we show that influenza A- or Sendai virus-infected human macrophages produce MIP-1alpha, MIP-1beta, RANTES, MCP-1, MCP-3, MIP-3alpha, IP-10, and IL-8, whereas no upregulation of MIP-3beta, eotaxin, or MDC production was detected. Influenza A virus was a better inducer of MCP-1 and MCP-3 production than Sendai virus, whereas MIP-1alpha, MIP-1beta, RANTES, MIP-3alpha, and IL-8 were induced preferentially by Sendai virus. Infection in the presence of protein synthesis inhibitor indicated that ongoing protein synthesis was required for influenza A virus-induced expression of MCP-1, MCP-3, and IP-10 genes, whereas Sendai virus-induced chemokine mRNA expression took place in the absence of de novo protein synthesis. Neutralization of virus-induced IFN-alpha/beta resulted in downregulation of virus-induced IP-10, MCP-1, and MCP-3 mRNA expression. IFN-alpha or IFN-gamma were found to directly enhance MCP-1, MCP-3, and IP-10 mRNA expression. Both influenza A and Sendai viruses similarly activated transcription factor NF-kappaB. In contrast to NF-kappaB, IRFs and STATs, the other transcription factors involved in the regulation of chemokine gene expression, were differentially activated by these viruses. Influenza A virus more efficiently activated ISGF3 complex formation and Stat1 DNA-binding compared to Sendai virus, which in turn was a more potent activator of IRF-1. Our results show that during viral infections macrophages predominantly produce monocyte and Th1 cell attracting chemokines. Furthermore, virus-induced IFN-alpha/beta enhanced chemokine gene expression in macrophages emphasizing the role of IFN-alpha/beta in the development of Th1 immune responses.
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PMID:Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. 1102 2

Influenza A virus causes respiratory tract infections, which are occasionally complicated by secondary bacterial infections. Influenza A virus replicates in epithelial cells and leukocytes resulting in the production of chemokines and cytokines, which favor the extravasation of blood mononuclear cells and the development of antiviral and Th1-type immune response. Influenza A virus-infected respiratory epithelial cells produce limited amounts of chemokines (RANTES, MCP-1, IL-8) and IFN-alpha/beta, whereas monocytes/macrophages readily produce chemokines such as RANTES, MIP-1alpha, MCP-1, MCP-3, IP-10 and cytokines TNF-alpha, IL-1beta, IL-6, IL-18 and IFN-alpha/beta. The role of influenza A virus-induced inflammatory response in relation to otitis media is being discussed.
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PMID:Inflammatory responses in influenza A virus infection. 1116 60

Sambucus nigra L. products - Sambucol - are based on a standardized black elderberry extract. They are natural remedies with antiviral properties, especially against different strains of influenza virus. Sambucol was shown to be effective in vitro against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, Sambucol reduced the duration of flu symptoms to 3-4 days. Convalescent phase serum showed a higher antibody level to influenza virus in the Sambucol group, than in the control group. The present study aimed to assess the effect of Sambucol products on the healthy immune system - namely, its effect on cytokine production. The production of inflammatory cytokines was tested using blood - derived monocytes from 12 healthy human donors. Adherent monocytes were separated from PBL and incubated with different Sambucol preparations i.e., Sambucol Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System and Sambucol for Kids. Production of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8) was significantly increased, mostly by the Sambucol Black Elderberry Extract (2-45 fold), as compared to LPS, a known monocyte activator (3.6-10.7 fold). The most striking increase was noted in TNF-alpha production (44.9 fold). We conclude from this study that, in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations activate the healthy immune system by increasing inflammatory cytokine production. Sambucol might therefore be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases. Sambucol could also have an immunoprotective or immunostimulatory effect when administered to cancer or AIDS patients, in conjunction with chemotherapeutic or other treatments. In view of the increasing popularity of botanical supplements, such studies and investigations in vitro, in vivo and in clinical trials need to be developed.
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PMID:The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. 1139 18

It was observed that interferon beta (IFN-beta) prevents the down-regulation of the interleukin-3 receptor alpha chain (IL-3Ralpha), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-beta-treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-beta and IL-3 acquire a dendritic morphology and express high levels of HLA antigen class I and class II and costimulatory molecules. When stimulated by either lipopolysaccharide or fibroblasts expressing CD40 ligand (CD40L) transfectants, dendritic cells (DCs) generated in IFN-beta and IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factor-alpha but low levels of IL-12 in comparison with DCs generated in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In mixed leukocyte culture, IL-3-IFN-beta DCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFN-gamma and IL-5 by naive adult CD4+ T cells. Finally, IL-3-IFN-beta DCs were found to produce much higher levels of IFN-alpha than IL-4-GM-CSF DCs in response to Poly (I:C) but not to influenza virus. It was concluded that monocytes cultured in the presence of IL-3 and IFN-beta differentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12.
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PMID:Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties. 1180 4

Monocytes/macrophages are highly susceptible to an infection with influenza A virus. After infection, de novo virus protein synthesis is detectable but rapidly interrupted before completion of the first viral replication cycle. Within 24-48 hours the infected monocytes die by apoptosis. Before cell death, infected monocytes initiate a cell-specific immune response. This includes the transcription and subsequent release of TNF-alpha (tumor necrosis factor alpha), IL-1beta (Interleukin 1beta), IL-6, type I inferferons and CC chemokines. Enhanced cytokine mRNA expression is due to a prolonged mRNA stability and an augmented gene transcription. Activation of transcription factors such as NF-kappaB (nuclear factor kappaB) and AP-1 are involved in activation of cytokine mRNA transcription. Infection of monocytes with influenza A virus induces the selective expression of mononuclear leukocyte attracting chemokines, such as MCP-1 (monocyte chemotactic protein 1), MIP-1alpha (macrophage inflammatory protein 1alpha) and RANTES (regulated upon activation, normal T cell expressed and secreted). In striking contrast, the release of the neutrophil-specific chemokines IL-8 (interleukin 8) and GRO-alpha (growth stimulatory activity alpha) is entirely suppressed. This differentially regulated chemokine expression may explain the mononuclear cell infiltrate characteristic for virus-infected tissue. Thus, infection of monocytes/macrophages with influenza A virus primes for a rapid proinflammatory reaction and induces an enhanced immigration of mononuclear cells into infected tissue. Taken together, these mechanisms may prepare the infected host for a fast and virus-specific immune response.
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PMID:Defense against influenza A virus infection: essential role of the chemokine system. 1184 25


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