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)

Human alveolar macrophages (AM) are susceptible to infection with respiratory syncytial virus (RSV), but the infection is abortive after the initial cycles of virus replication. We have investigated if RSV infection of AM results in the production of cytokines TNF, IL-6, and IL-8, all of which may modulate inflammatory and immune responses to the virus, as well as may directly protect respiratory epithelial cells against spread of infection. Within 1 h after interaction with RSV, increased mRNA levels were found for all three cytokines. Peak expression of the mRNAs occurred at 3 to 6 h. The virus most effectively induced TNF mRNA expression greater than IL-6 mRNA greater than IL-8 mRNA, as compared to cytokine mRNA expression induced by bacterial endotoxin. Inactivated virus was almost as effective as live virus in inducing and maintaining increased IL-6 and IL-8 mRNA over 16 h, whereas live infectious RSV was necessary for maintaining TNF mRNA expression over the same time. Protein concentrations of the different cytokines in the supernatants of infected AM reflected the increased levels of mRNA in the cells. Despite the high levels of cytokines with possible antiviral activity (TNF and IL-6) in the AM supernatants, neither supernatants nor rTNF when added to bronchial epithelial cells protected them from infection with RSV. However, TNF, IL-1, and RSV, but not IL-6, induced IL-8 and IL-6 mRNA expression by the bronchial epithelial cells suggesting that cytokines produced by RSV-infected AM may be more important in modulating the inflammatory response in infection than directly interfering with virus infection/replication of airway epithelium.
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PMID:Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. 175 1

Respiratory syncytial virus (RSV) preferentially infects respiratory epithelium and is an important cause of lower respiratory tract infections in young children. RSV induces the production of interleukin (IL)-8 in airway epithelial cells; however, the mechanism of this induction is not known. To define the mechanism by which RSV induces IL-8 gene activation, A549 epithelial cells were transfected with plasmids containing serial deletions of the 5'-flanking region of the IL-8 gene and then exposed to RSV for 24 h. A positive cooperative effect of the binding sites for the transcription factors, nuclear factor (NF)-kappa B and NF-IL-6, was observed. Mutations in either region abates responsiveness of the promoter to RSV infection. RSV also increases activation of the NF-kappa B and NF-IL-6 transcription factors. These data suggest that RSV may increase IL-8 production in airway epithelium partly via activation of the transcription factors NF-kappa B and NF-IL-6.
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PMID:Induction of interleukin (IL)-8 gene expression by respiratory syncytial virus involves activation of nuclear factor (NF)-kappa B and NF-IL-6. 869 53

Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children. RSV preferentially infects airway epithelium and causes local production of inflammatory cytokines. Ribavirin, the only specific agent available for treatment of RSV infection, has limited effectiveness. There are few data regarding the ability of drugs to modulate the inflammatory response of epithelium infected with RSV. This study evaluated the effect of amiloride and ribavirin on cytokine production by RSV-infected epithelium. We observed a dose-dependent reduction in interleukin (IL)-8 protein release with both amiloride and ribavirin in RSV-infected A549 epithelial cells. Peak effects were observed at concentrations of 200 microM amiloride and 60 microM ribavirin. Both amiloride and ribavirin inhibited IL-8 mRNA induction. Pretreatment with either agent was not required to inhibit IL-8 release. Both drugs also inhibited IL-6 release. However, unlike ribavirin, amiloride did not inhibit viral replication or infection. Amiloride also inhibited IL-8 release from A549 cells stimulated with IL-1 or tumor necrosis factor. Amiloride similarly inhibited IL-8 protein release from primary human airway epithelium infected with RSV. These data demonstrate that both amiloride and ribavirin inhibit cytokine production in RSV-infected airway epithelium. These results suggest amiloride, as well as ribavirin, may be useful as a therapeutic agent in RSV infections.
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PMID:Amiloride inhibits cytokine production in epithelium infected with respiratory syncytial virus. 877 57

The presence of histamine and eosinophil cationic protein in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV)-induced bronchiolitis implies the activation of basophil and eosinophil leukocytes, but the specific mechanism of their recruitment has not been elucidated. Chemokines are potent and selective leukocyte chemotactic molecules that are also expressed by airway epithelial cells. Therefore, the pattern of chemokines produced in response to RSV infection was investigated in primary cultures of human nose- and adenoid-derived epithelial cells. Interleukin-8, growth-related peptide-alpha, and monocyte chemotactic protein-1 were constitutively released by uninfected epithelial cells and were not further enhanced by infection with RSV. RANTES (regulated upon activation, normal T cell-expressed and -secreted), which was present in negligible concentrations in uninfected cultures, was strongly induced by RSV infection, in a dose- and time-dependent manner. Through the release of RANTES, epithelial cells may control the selective concentration and activation of basophils and eosinophils in RSV-infected airway mucosa.
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PMID:Respiratory syncytial virus induces selective production of the chemokine RANTES by upper airway epithelial cells. 904 19

Infection of the lung epithelial cell line A549 by respiratory syncytial virus (RSV) resulted in the elevated synthesis of multiple cellular cytokines, including a number of interleukins (ILs). Detailed studies of IL-11 induction revealed that it required infection by viable virus and involved a net increase in the steady state level of IL-11 mRNA. Nuclear run-on assays showed a direct effect of RSV on IL-11 gene transcription. Mutational analysis of the IL-11 promoter fused to a reporter luciferase gene demonstrated the requirement of a region 720 nucleotides upstream of the mRNA start site in the transcriptional induction of IL-11 by RSV. Two nearly identical 10-nucleotide-long sequences GGGGTCTCCC and GGGTCTCCCC in this region resembled the NF-kappa B consensus motif. Mutation of either sequence greatly reduced RSV-mediated induction of IL-11 promoter activity. NF-kappa B sites in IL-1 alpha, IL-6, and IL-8 promoters were also required for RSV-mediated induction of transcription of these promoters. Immunological studies and use of reporter gene constructs provided direct evidence for the activation and nuclear translocation of NF-kappa B by RSV. Sodium salicylate and aspirin, inhibitors of NF-kappa B activation, abolished transcriptional induction of all these cytokines by RSV. Together, these studies demonstrated an essential role of NF-kappa B in RSV-mediated transcription of multiple cytokines genes and suggested a possible use of salicylates in managing airway inflammation and viral pathogenesis during RSV infection.
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PMID:Transcriptional induction of multiple cytokines by human respiratory syncytial virus requires activation of NF-kappa B and is inhibited by sodium salicylate and aspirin. 919 51

The role of "oxidant-sensitive" transcription factors activator protein (AP)-1, nuclear factor (NF)-kappaB, and NF-IL6 in respiratory syncytial virus (RSV)-induced interleukin (IL)-8 gene expression in A549 epithelial cells was evaluated. RSV infection resulted in increased binding of each of these transcription factors. Transfection of A549 cells with plasmids containing serial truncations of the 5'-flanking region of the IL-8 gene revealed a positive cooperative effect of the binding sites for AP-1 and NF-kappaB. Mutation of either region markedly diminished responsiveness of the promoter to RSV. Mutation of the NF-IL6 site had minimal effect in the presence of intact binding sites for NF-kappaB and AP-1. The antioxidants NAC (N-acetylcysteine), DMSO, and DMPO (5,5-dimethyl-1-pyrroline N-oxide) did not inhibit RSV-induced binding of NF-kappaB; however, binding of AP-1 and NF-IL6 was inhibited. These observations suggest that AP-1 may be the preferred transcription factor (over NF-IL6) for cooperative interaction with NF-kappaB in RSV-induced IL-8 production.
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PMID:Activator protein-1 is the preferred transcription factor for cooperative interaction with nuclear factor-kappaB in respiratory syncytial virus-induced interleukin-8 gene expression in airway epithelium. 959 12

Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes that cause farmer's lung disease. The early response to Ag is an increase in neutrophils in the lung, whereas the late response is a typical Th1-type granulomatous disease. Many patients who develop disease report a recent viral respiratory infection. These studies were undertaken to determine whether viruses can augment the inflammatory responses in HP. C57BL/6 mice were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) for 3 consecutive days per wk for 3 wk. Some mice were exposed to SR at 2 wk after infection with respiratory syncytial virus (RSV), whereas others were exposed to SR after exposure to saline alone or to heat-inactivated RSV. SR-treated mice developed a typical, early neutrophil response and a late granulomatous inflammatory response. Up-regulation of IFN-gamma and IL-2 gene expression was also found during the late response. These responses were augmented by recent RSV infection but not by heat-inactivated RSV. Mice with a previous RSV infection also had a greater early neutrophil response to SR, with increased macrophage inflammatory protein-2 (MIP-2, murine equivalent of IL-8) release in bronchoalveolar lavage fluid. These studies suggest that viral infection can augment both the early and late inflammatory responses in HP.
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PMID:Viral infection modulates expression of hypersensitivity pneumonitis. 1035 92

Nitrogen dioxide (NO(2)) is a common air pollutant outdoors and indoors in homes with unvented combustion sources. It is also a constituent of tobacco smoke. Epidemiological studies suggest that children exposed to NO(2), or living with smoking parents, have an increased incidence of respiratory viral infections. The most common virus causing severe respiratory symptoms in infants and young children is respiratory syncytial virus (RSV). In the present study we investigated whether NO(2) exposure affects RSV infection in airway epithelial cells, the host cells for viral replication and virus-induced cytokine production. Cultures of the bronchial epithelial cell line BEAS-2B exposed to 0.5, 1.0, and 1.5 ppm NO(2) for 60 min were infected with RSV. Viral replication, as well as RSV-induced interleukin (IL)-6 and IL-8, was assessed at various times postinfection. The NO(2) doses used were not toxic to the BEAS-2B cells as measured by release of lactic dehydrogenase (LDH). The internalization of RSV was increased by exposure to 0.5 ppm NO(2) and decreased by exposure to 1.5 ppm NO(2). On the other hand, the release of infectious virus 48 h postexposure was not affected by the two lower doses of NO(2), but was significantly reduced in cells exposed to 1.5 ppm NO(2). Virus-induced cytokine production was also significantly reduced in cells exposed to 1.5 ppm NO(2), and not affected by 0.5 and 1.0 ppm. It is likely that the decrease in cytokine production is related to the decrease in viral burden. These data suggest that possible increases in viral clinical symptoms associated with NO(2) may not be caused by increased susceptibility of the epithelial cells to infection but may result from effects of NO(2) on host defenses that prevent the spread of virus.
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PMID:Effect of nitrogen dioxide on respiratory viral infection in airway epithelial cells. 1043 48

Epidemiology studies associate increased pulmonary morbidity with episodes of high particulate air pollution (size range 0.1-10 microm diameter, PM10). Pneumonia, often viral in origin, is increased following episodes of high PM10 pollution. Therefore, this study was undertaken to investigate how PM10 alters airway inflammatory responses to respiratory syncytial virus (RSV), a frequent cause of viral pneumonia in infants and the elderly. Supernatants of unexposed and PM10-exposed alveolar macrophage (AM) cultured with uninfected or RSV-infected airway epithelial cells were assessed for a number of chemokines responsible for inflammatory responses in the lung. AM exposure to PM10 in the absence of infection resulted in a significant increase in interleukin (IL)-8 and macrophage inflammatory protein (MIP)-1alpha production but not in MIP-1beta or monocyte chemotactic protein (MCP)-1. AM responded to RSV infection by the production of IL-8, MIP-1alpha, MIP-1beta, and MCP-1, while RANTES was derived solely from the RSV-infected bronchial epithelial cell line BEAS-2B. In the presence of PM10, the AM response to RSV was blunted. RSV-induced MCP-1 was significantly decreased, and the levels of MIP-1 and IL-8 were lower than expected from a combined response to PM10 and RSV. Furthermore, AM analyzed for uptake of virus showed a 50% decrease in viral antigen when exposed to PM10 RSV-induced production of RANTES by epithelial cells was decreased in the presence of AM but not affected by PM10 exposure. Taken together, these results suggest that AM-regulated inflammatory responses to viral infection are altered by exposure to PM10 in a manner that may result in increased spread of infection and thus may increase viral pneumonia-related hospital admissions.
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PMID:Exposure to urban air particulates alters the macrophage-mediated inflammatory response to respiratory viral infection. 1049 14

Respiratory syncytial virus (RSV) produces intense pulmonary inflammation, in part, through its ability to induce chemokine synthesis in infected airway epithelial cells. In this study, we compare mechanisms for induction of the CXC chemokine IL-8, in human type II alveolar (A549) cells by RSV infection and by stimulation with the cytokine TNF. Promoter deletion and mutagenesis experiments indicate that although the region from -99 to -54 nt is sufficient for TNF-induced IL-8 transcription, this region alone is not sufficient for RSV-induced IL-8 transcription. Instead, RSV requires participation of a previously unrecognized element, spanning from -162 to -132 nt, that we term the RSV response element (RSVRE), and a previously characterized element at -132 to -99 nt, containing an AP-1 binding site. RSV infection of A549 cells induces increased RSVRE- and AP-1-binding activities and increased synthesis of IFN regulatory factor-1 protein, which is present in the RSVRE-binding complex. These data confirm that the IL-8 gene enhancers are controlled in a stimulus-specific fashion and participation of distinct promoter elements is required to activate gene transcription. These observations are important for rational design of inhibitors of RSV-induced lung inflammation.
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PMID:Requirement of a novel upstream response element in respiratory syncytial virus-induced IL-8 gene expression. 1082 Feb 77


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