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)

The mechanisms leading to the severe lung damage seen in some sheep naturally infected with the visna-maedi virus, and to pulmonary lesions in other lentiviral diseases, appear to involve the recruitment of large numbers of uninfected inflammatory cells. Only a few alveolar macrophages from experimentally infected lambs express virus, but high levels of interleukin (IL)-8 mRNA are present in the macrophage population. In vitro infection with visna-maedi virus at low multiplicity of alveolar macrophages from uninfected sheep also strongly induced the expression of IL-8 mRNA and the accumulation of IL-8 in the extracellular medium. An initial peak of IL-8 mRNA expression at 3 or 6 h after infection was followed by a fall, then a more persistent expression lasting at least 48 h after infection. The early peak was accompanied by expression of mRNA for IL-1beta, and a possible rise in tumor necrosis factor alpha (TNFalpha) mRNA, although this was frequently elevated in uninfected ovine alveolar macrophages. Interestingly, these events occurred identically in cells treated with non-infectious heat-treated virus, suggesting that interaction between viral components and cellular membrane receptors could suffice for both early and late IL-8 induction. The level of IL-8 mRNA induced by treatment with live or inactivated virus could be severely reduced by pretreatment of the macrophages with genistein but not with staurosporine, suggesting the involvement of a tyrosine-kinase signaling pathway. The early induction of IL-1beta and possibly of TNFalpha may explain the occurrence of a later persistent expression of IL-8 mRNA through an autocrine mechanism.
Am J Respir Cell Mol Biol 1998 Apr
PMID:Visna-maedi virus induces interleukin-8 in sheep alveolar macrophages through a tyrosine-kinase signaling pathway. 953 41

Interleukin-8 (IL-8) is a cytokine, which possesses both chemotactic and activating properties for neutrophils, lymphocytes and basophils. Various evidence has indicated IL-8 to be implicated in the pathophysiology of immune-mediated renal diseases. We thus examined the expression of IL-8 in renal diseases. We detected the expression of IL-8 both in mRNA and the protein levels in renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis. A significant correlation was found between the expression of IL-8 mRNA and the number of neutrophils in the glomerulus. We also found a negative correlation between the expression of IL-8 mRNA and creatinine clearance. Our study thus suggested IL-8 to be involved in the pathophysiology of proliferative glomerulonephritis.
Res Commun Mol Pathol Pharmacol 1998 Feb
PMID:Expression of interleukin-8 in human glomerulonephritis. 958 95

Most strains of Helicobacter pylori from patients with peptic ulcer disease or intestinal-type gastric cancer carry cagA, a gene that encodes an immunodominant protein of unknown function, whereas many of the strains from asymptomatically infected persons lack this gene. Recent studies showed that the cagA gene lies near the right end of a approximately 37kb DNA segment (a pathogenicity island, or PAI) that is unique to cagA+ strains and that the cag PAI was split in half by a transposable element insertion in the reference strain NCTC11638. In complementary experiments reported here, we also found the same cag PAI, and sequenced a 39 kb cosmid clone containing the left 'cagII' half of this PAI. Encoded in cagII were four proteins each with homology to four components of multiprotein complexes of Bordetella pertussis ('Ptl'), Agrobacterium tumefaciens ('Vir'), and conjugative plasmids ('Tra') that help deliver pertussis toxin and T (tumour inducing) and plasmid DNA, respectively, to target eukaryotic or prokaryotic cells, and also homologues of eukaryotic proteins that are involved in cytoskeletal structure. To the left of cagII in this cosmid were genes for homologues of HsIU (heat-shock protein) and Era (essential GTPase); to the right of cagII were homologues of genes for a type I restriction endonuclease and ion transport functions. Deletion of the cag PAI had no effect on synthesis of the vacuolating cytotoxin, but this deletion and several cag insertion mutations blocked induction of synthesis of proinflammatory cytokine IL-8 in gastric epithelial cells. Comparisons among H. pylori strains indicated that cag PAI gene content and arrangement are rather well conserved. We also identified two genome rearrangements with end-points in the cag PAI. One, in reference strain NCTC11638, involved IS605, a recently described transposable element (as also found by others). Another rearrangement, in 3 of 10 strains tested (including type strain NCTC11637), separated the normally adjacent cagA and picA genes and did not involve IS605. Our results are discussed in terms of how cag-encoded proteins might help trigger the damaging inflammatory responses in the gastric epithelium and possible contributions of DNA rearrangements to genome evolution.
Mol Microbiol 1998 Apr
PMID:Analyses of the cag pathogenicity island of Helicobacter pylori. 959 95

Inflammatory pseudotumour of the lung is a lesion mainly composed of histiocytes. Histiocyte accumulation may arise from local proliferation of migratory cells, from cytokine induced recruitment of monocytes from the systemic circulation, or both. Cell proliferation was investigated with Ki-67 immunostaining and cytokine production with reverse transcriptase-polymerase chain reaction in two cases of inflammatory pseudotumour of the lung. It was found that the two lesions were composed mainly of non-proliferating (Ki-67 non-binding) macrophages that stained positive for CD68, CD14, CD4, and mannose receptor. Both cases contained mRNA transcripts for monocyte chemotactic protein-1 (MCP-1), a monocyte chemoattractant, and for interleukin 6 (IL-6), an inducer of plasma cell differentiation. One of the two cases also contained mRNA transcripts for IL-8, a neutrophil chemoattractant. These findings are consistent with the possibility that accumulation of non-proliferating histiocytes induced by MCP-1 is one of the pathogenic events occurring in inflammatory pseudotumour of the lung.
Mol Pathol 1998 Feb
PMID:Monocyte chemotactic protein-1 in the inflammatory pseudotumour of the lung. 962 22

Fine particles in the air have been associated with increased mortality and morbidity. Particulate air pollution is a complex mixture which varies by region and includes a number of components including residual oil fly ash (ROFA), a byproduct of power plant and industry fuel-oil combustion. Human airway epithelial cells exposed to ROFA release inflammatory cytokines including interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is dependent upon pretranscriptional binding of cis regulatory elements, including nuclear factor kappaB (NF-kappaB). To investigate the role of NF-kappaB in the particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS-2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6 messenger RNA (mRNA), which was preceded by the activation of nuclear proteins binding to the NF-kappaB sequence motif in the IL-6 promoter. Transient transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked to a luciferase reporter gene confirmed that NF-kappaB binding is necessary for the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine, suggesting that the activation of NF-kappaB may be mediated through reactive oxygen intermediates generated by transition metals found in ROFA. Activation of NF-kappaB may therefore be a critical first step in the inflammatory cascade following exposure to particles generated by oil combustion.
Am J Respir Cell Mol Biol 1998 Jul
PMID:Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation. 965 Nov 85

High levels of neutrophils and the neutrophil-attracting chemokine interleukin (IL)-8 have been observed in the airways of patients with cystic fibrosis (CF). We hypothesized that CF respiratory epithelium produces excessive amounts of IL-8 either at baseline or after stimulation. To test this hypothesis we compared immunoreactive IL-8 release by primary nasal epithelial cell (NEC) cultures established from young children with or without CF, at several time points after stimulation of cultures with tumor necrosis factor-alpha (TNF-alpha) or infection with respiratory syncytial virus (RSV). Both stimuli induced significantly increased IL-8 release by both CF and control cultures. However, there was no difference between CF and control cells in either the magnitude or duration of the IL-8 response. The effect of transduction of CF cells with Ad5-CBCFTR, an adenovirus vector mediating expression of cystic fibrosis transmembrane regulator (CFTR), on IL-8 production was also determined. TNF-alpha stimulated IL-8 production was not different in Ad5-CBCFTR-transduced, -untransduced, or Ad5-CMVLacZ-transduced control cells. Lastly, immortalized CF tracheal epithelial cell lines, both uncorrected and retrovirally corrected with CFTR, were compared. Again, TNF-alpha-stimulated IL-8 production did not differ significantly between cell lines with and without functioning CFTR. Our data suggest that isolated CF NECs cultured under these conditions do not produce more IL-8 than do non-CF control cultures, either at baseline or after incubation with the nonspecific stimuli TNF-alpha and RSV. We conclude that the absence of functioning CFTR alone is not sufficient to cause excessive production of IL-8.
Am J Respir Cell Mol Biol 1998 Aug
PMID:Interleukin-8 production by cystic fibrosis nasal epithelial cells after tumor necrosis factor-alpha and respiratory syncytial virus stimulation. 969 92

Particulate air pollution causes increased cardiopulmonary morbidity and mortality, but the chemical determinants responsible for its biologic effects are not understood. We studied the effect of total suspended particulates collected in Provo, Utah, an area where an increase in respiratory symptoms in relation to levels of particulate pollution has been well documented. Provo particulates caused cytokine-induced neutrophil chemoattractant-dependent inflammation of rat lungs. Provo particulates stimulated interleukin-6 (IL-6) and IL-8 production, increased IL-8 messenger RNA (mRNA) and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured BEAS-2B cells, and stimulated IL-8 secretion in primary cultures of human bronchial epithelium. Cytokine secretion was preceded by activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and was reduced by treatment of cultures with superoxide dismutase, deferoxamine, or N-acetylcysteine. These biologic effects were replicated by culturing BEAS cells with quantities of Cu2+ found in Provo extract. IL-8 secretion by BEAS cells could be modified by addition of normal constituents of airway lining fluid to the culture medium. Mucin significantly reduced IL-8 secretion, and ceruloplasmin significantly increased IL-8 secretion and activation of NF-kappaB. These findings suggest that copper ions may cause some of the biologic effects of inhaled particulate air pollution in the Provo region of the United States, and may provide an explanation for the sensitivity of asthmatic individuals to Provo particulates that has been observed in epidemiologic studies.
Am J Respir Cell Mol Biol 1998 Sep
PMID:Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution. 973 Aug 64

The capacity of Mycobacterium tuberculosis (MTB) to induce production of chemokines with known chemotactic activity for monocytes and lymphocytes, the cellular building blocks of granulomas, was investigated. These chemokines included regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha). MTB stimulated production of MCP-1 and MIP-1alpha by blood monocytes (MN) and alveolar macrophages (AM). MTB infection of MN and AM stimulated release but not production of RANTES. AM produced or released significantly higher levels than MN of RANTES (by 2.1-fold), MCP-1 (by 6.9-fold), and MIP-1alpha (by 5. 5-fold) (P < 0.05 for each). This study also confirmed that MTB-infected AM produce the chemokine interleukin (IL)-8. MTB infection of AM resulted in increased steady-state expression of messenger RNA (mRNA) for MCP-1 and MIP-1alpha and minimal increased expression of RANTES mRNA. Both an avirulent (H37Ra) and a virulent (H37Rv) strain of MTB and purified protein derivative of H37Rv but not latex beads induced production of chemokines. Supernatants of MTB-infected cells demonstrated chemotactic activity for both monocytes and lymphocytes partially inhibitable by neutralizing antibodies against the chemokines studied. Bronchoalveolar lavage fluid from patients with active pulmonary tuberculosis as compared with healthy control subjects contained increased levels of RANTES (by 8-fold), MCP-1 (by 2.7-fold), and IL-8 (by 8.9-fold) (P < 0.05), but not MIP-1alpha, as compared with healthy control subjects. Thus, multiple chemokines may be involved in recruitment of cells for granuloma formation in tuberculosis.
Am J Respir Cell Mol Biol 1998 Sep
PMID:Chemokines induced by infection of mononuclear phagocytes with mycobacteria and present in lung alveoli during active pulmonary tuberculosis. 973 Aug 80

Recently, some investigators have observed elevated concentrations of chloride in the airway surface fluid (ASF) overlying respiratory epithelia from cystic fibrosis (CF) patients compared with ASF overlying non-CF epithelia. Others have shown that this elevated ASF salt concentration can inactivate human beta-defensin-1, an antimicrobial peptide secreted by respiratory epithelia. This could impair the primary epithelial defense against bacteria in the CF airway, thereby forcing a greater reliance on polymorphonuclear leukocyte (PMN)-mediated defenses. Pseudomonas aeruginosa (Psa) flourishes in the CF airway despite the presence of abundant PMN. We therefore investigated whether elevated ASF chloride concentration in CF might also compromise PMN function. We employed a cell-culture model in which halide concentrations and osmolarity were varied independently. We examined the effects of chloride concentration on three aspects of PMN function: recruitment of PMN to the airway (production of interleukin-8 [IL-8]), PMN antimicrobial activity (killing of Psa), and PMN clearance from the airways (apoptosis and lysis). We found that exposure to elevated chloride concentration increased PMN synthesis of IL-8, decreased PMN killing of Psa, and accelerated PMN apoptosis and lysis. In CF airways, elevated chloride therefore could contribute to the increased number of PMN recruited into the airways, the increased survival of Psa, and the increased quantity of toxic mediators released by PMN into the airways. These effects of elevated chloride on PMN function may provide another causal link between loss of cystic fibrosis transmembrane conductance regulator function and CF lung disease.
Am J Respir Cell Mol Biol 1998 Oct
PMID:The effect of chloride concentration on human neutrophil functions: potential relevance to cystic fibrosis. 976 62

The obligate intracellular pathogen Chlamydia pneumoniae is associated with chronic respiratory, atherosclerotic, and rheumatic disease. The alveolar macrophage (AM) is a potential target cell for the pathogen and may contribute to respiratory immunopathology. We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C. pneumoniae and AM from 12 healthy volunteers. Inflammatory responses were evaluated through lucigenin-amplified chemiluminescence; secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin 8 (IL-8); and expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen-DR (HLA-DR). C. pneumoniae readily induced productive infection in the AM. Inclusions containing replicating pathogens could be maintained for up to 120 h. Morphologically similar infection patterns were seen ex vivo in AM collected from six patients with known C. pneumoniae pneumonia. AM responded to the infection with a marked, dose-dependent release of reactive oxygen species, TNF-alpha, IL-1beta, and IL-8. ICAM-1 expression remained unchanged, but HLA-DR was significantly upregulated. Our data indicate that the release of antimicrobial mediators cannot prevent chlamydial infection and replication in AM, but may be involved in amplification of the local inflammatory response in C. pneumoniae pneumonia.
Am J Respir Cell Mol Biol 1998 Nov
PMID:Interaction of Chlamydia pneumoniae and human alveolar macrophages: infection and inflammatory response. 980 36


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