Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies demonstrated that respiratory syncytial virus (RSV) infection of A549 cells induced interleukin (IL)-8 gene expression and protein release from the cells as early as 2 h after treatment [M. A. Fiedler, K. Wernke-Dollries, and J. M. Stark. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L865-L872, 1995; J. G. Mastronarde, M. M. Monick, and G. W. Hunninghake. Am. J. Respir. Cell Mol. Biol. 13: 237-244, 1995]. Furthermore, the effects of RSV at the 2-h time point were not dependent on viral replication. The studies reported here were designed to test the hypothesis that active and inactive RSV induce IL-8 gene expression in A549 cells at the 2-h time point by a mechanism dependent on the activation of the nuclear transcription factor NF-kappa B Northern blot analysis indicated that IL-8 gene expression occurred independent of protein synthesis 2 h after A549 cells were treated with RSV. Analysis of nuclear extracts from RSV-treated A549 cells by electrophoretic mobility shift assays demonstrated that NF-kappa B was activated as early as 15 min after RSV was added to the cells and remained activated for at least 90 min. In contrast, baseline levels of NF-IL-6 and activator protein-1 (AP-1) did not change over this period of time. Deoxyribonuclease footprint analysis of a portion of the 5'-flanking region of the IL-8 gene demonstrated two potential regions for transcription factor binding, which corresponded to the potential AP-1 binding site, and potential NF-IL-6 and NF-kappa B binding sites. Mutational analysis of the 200-bp 5'-untranslated region of the IL-8 gene demonstrated that activation of NF-kappa B and NF-IL-6 were required for RSV-induced transcriptional activation of the IL-8 gene.
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PMID:Mechanism of RSV-induced IL-8 gene expression in A549 cells before viral replication. 899 67

Cardiac inflammatory responses appear to play a pivotal role in scar formation after acute myocardial infarction. Monocyte chemotactic and activating factor (MCAF) monocyte chemoattractant protein-1 (MCP-1) is a cytokine with chemotactic activity for mononuclear phagocytes, but also for NK cells, T cells, mast cells, and basophils. To investigate the possible involvement of MCAF/MCP-1 in the pathogenesis, its course was studied in patients with acute myocardial infarction. Twenty-three consecutive patients with acute myocardial infarction and 18 patients with angina pectoris were studied. Cytokines were measured by enzyme-linked immunosorbent assay. Plasma levels of interleukin IL-1alpha, IL-1beta, and IL-2 were below the detection limit of our method. IL-6 and interferon-gamma were detected in 17.4%, and tumor necrosis factor-alpha in 13.0% of patients with acute myocardial infarction, but the frequency was not statistically significantly different from that in angina pectoris. The plasma level of MCAF/MCP-1 in myocardial infarction tended to increase at 3 h after the onset of chest pain (133 +/- 19 pg/ml, P= 0.06) and was significantly elevated at 9 h (143 +/- 20 pg/ml) when compared with that in angina pectoris (87 +/- 6 pg/ml, P<0.05). The MCAF/MCP-1 level remained increased during the 24-hours observation period (P<0.01), and maximum level (168 +/- 13 pg/ml) was seen at 24 hour. The level of MCAF/ MCP-1 correlated significantly with the plasma level of another chemokine, IL-8, at 12 h after the onset of chest pain (r=0.51, P<0.05), suggesting that common stimuli mediate the release of both cytokines in myocardial infarction. The identification of MCAF/MCP-1 as an inflammatory mediator in acute myocardial infarction suggests that mononuclear phagocytes may play an important role in the early stage of the disease.
J Mol Cell Cardiol 1997 Jan
PMID:Plasma levels of the monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 are elevated in patients with acute myocardial infarction. 904 55

To elucidate the pathogenetic mechanism of renal parenchymal injury in autosomal dominant polycystic kidney disease (ADPKD) patients, typically characterized by renal cystic changes paralleled by interstitial inflammation and gradual fibrotic changes, the role of selected inflammatory mediators was evaluated in a group of ADPKD patients with normal glomerular filtration rate. The plasma concentrations of IL-6, IL-8, ICAM-1 and VCAM-1 (which may reflect systemic response to inflammation/infection) were increased in the ADPKD patient group. Coupled with decreased urinary excretion of the IL-1 receptor antagonist (which exerts an anti-inflammatory role), these results suggest that even in overt infection free status, the proinflammatory system is more activated and anti-inflammatory defence system weakened in ADPKD subjects. Our data support the current view that cytokines are candidate contributors to pathogenesis of ADPKD.
Biochem Mol Biol Int 1997 Mar
PMID:Cytokine profile in autosomal dominant polycystic kidney disease. 909 Apr 70

A profound inflammatory response is initiated immediately following traumatic brain injury (TBI) and is characterized by the release of several cytokines with pro- and anti-inflammatory functions. In order to elucidate which cytokines are released in the human brain in response to injury as well as in the peripheral compartment, IL-1, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta were monitored in CSF and serum of severely brain-injured patients. Furthermore, we investigated the possible modulation of systemic reactions by IL-6 and the ability of IL-6 and IL-8 to promote the synthesis of nerve growth factor.
Mol Psychiatry 1997 Mar
PMID:Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. 910 36

Migration of eosinophils through the basement membrane barrier is an important step for their infiltration into tissues. To investigate the mechanism of transmigration, we used a chamber fitted with a Matrigel membrane as a model of the basement membrane. In this model, eosinophils treated with cytokines or chemotactic factors alone did not transmigrate from the upper to the lower chamber. However, platelet-activating factor (PAF) strongly induced transmigration of eosinophils stimulated by interleukin (IL)-5, indicating that both a cytokine and a chemotactic factor are required for eosinophil migration through Matrigel. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 also stimulated eosinophil transmigration in the presence of PAF. Of seven eosinophil chemotactic factors tested, leukotriene B4, C5a, RANTES, macrophage inflammatory protein-1alpha, and IL-8 did not induce significant eosinophil transmigration. Only PAF and eotaxin induced transmigration of eosinophils through Matrigel in the presence of IL-5; PAF was more potent than eotaxin at the optimal concentration. In contrast, PAF, eotaxin, and RANTES all potently induced migration of eosinophils through bare membrane in the absence of IL-5. Finally, eosinophil migration through Matrigel was markedly reduced by a combination of anti-CD18 and anti-CD29 monoclonal antibodies, suggesting that it is mediated by beta1- and beta2-integrin adhesion molecules. Our findings demonstrate that eosinophil transmigration through a basement membrane model requires both a specific chemoattractant, such as PAF, and an eosinophil-activating cytokine, such as IL-5. This synergistic effect is likely important in the tissue accumulation of activated eosinophils in allergic and other eosinophil-associated diseases.
Am J Respir Cell Mol Biol 1997 Apr
PMID:Transmigration of eosinophils through basement membrane components in vitro: synergistic effects of platelet-activating factor and eosinophil-active cytokines. 911 57

In type 1 Gaucher disease, decreased activity of glucocerebrosidase results in accumulation of glucosylceramide in macrophages. Infiltration of liver, spleen and bone marrow by lipid-laden macrophages leads to hepatosplenomegaly, bone lesions and cytopenia. These abnormal macrophages may produce and release macrophage derived factors and cytokines, which could contribute to the pathophysiology of the disease. Whether these cytokines and factors are elevated in Gaucher disease is currently unknown. In 29 type 1 Gaucher disease patients we measured serum levels of the macrophage derived cytokines IL8, IL6, TNFalpha, M-CSF and the monocyte/macrophage activation marker sCD14. These factors were studied in relation to disease severity and during treatment with enzyme supplementation therapy. Most patients showed remarkably elevated levels of M-CSF (2-8 fold) and sCD14 (2-5 fold) as compared to normal controls. Levels of IL8 were elevated in all patients (2-20 fold), whereas levels of IL6 and TNFalpha were normal. There was a significant correlation between severity of the disease as determined by the severity score index (SSI), and M-CSF, sCD14 and IL8 levels. M-CSF and sCD14 levels also correlated with the excess liver and spleen volumes. During treatment with alglucerase, levels of M-CSF and sCD14 declined, but IL8 remained unchanged. The relative reduction in excess liver and spleen volume did not correlate with the relative reduction in M-CSF or sCD14 levels. We conclude that serum levels of M-CSF, sCD14 and IL8 are increased in type 1 Gaucher disease. The biological activities of M-CSF and IL8 may add to the pathophysiology of the disease.
Blood Cells Mol Dis 1997 Aug
PMID:Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. 923 58

Interleukin-8 (IL-8) is a chemoattractant and activating factor for human neutrophlls and a potent angiogenic agent. The peritoneal fluid of women with endometriosis has been shown to have increased neutrophil chemotactic activity. We postulate that IL-8 may be an important modulator in the pathogenesis of endometriosis and adhesion formation. We first investigated IL-8 concentrations in the peritoneal fluid of women with or without endometriosis, then assessed peritoneal mesothelial cells as a potential source of peritoneal fluid IL-8. Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate IL-8 mRNA and protein modulation. The mean concentration of IL-8 in samples obtained from control patients (n = 28) was 4.8 +/- 0.5 pg/ml; from patients with minimal-mild endometriosis (n = 24) was 27.5 +/- 2.6 pg/ml; and from patients with moderate-severe endometriosis (n = 21) was 530.2 +/- 65.1 pg/ml. Confluent mesothelial cells were incubated with human recombinant IL-1 alpha (0.01-100 IU/ml) or tumour necrosis factor (TNF)-alpha (0.01 to 100 ng/ml) for 2-24 h. IL-8 mRNA was detectable in non-treated cells, however both IL-1 alpha and TNF-alpha induced higher amounts of IL-8 mRNA in a dose- and time-dependent manner. Non-treated mesothelial cells in culture also produced and secreted IL-8 protein quantified by ELISA, but again higher concentrations were induced by IL-1 alpha and TNF-alpha treatment. In conclusion, we found that IL-8 concentrations were elevated in peritoneal fluids from women with endometriosis. Cultured mesothelial cells expressed cytokine-inducible IL-8 mRNA and secreted IL-8 protein. The regulated expression of this angiogenic factor may play a role in pathogenesis of endometriosis.
Mol Hum Reprod 1996 Jan
PMID:Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells. 923 56

Intraovarian cytokines play a pivotal role in the normal growth and development of the ovarian follicle. The purpose of this study was to investigate the pattern of cytokine mRNA expression in ovarian endometriomata. A total of 10 patients with histologically confirmed endometriomata undergoing surgery formed the study group while nine patients undergoing sterilization with no evidence of a cyst in the ovary formed the control group. Biopsies of the ovary were obtained at surgery and stored in liquid nitrogen until processed by reverse transcription-polymerase chain reaction amplification to identify the presence of mRNA for interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). IL-6 and IL-10 mRNA were expressed by nine and seven patients respectively in the endometriosis group compared with three and one patients in the control group; this difference was significant (P < 0.05). IL-1 alpha mRNA was expressed by seven of 10 patients with endometriosis but by only one of the control group; this was again significantly different (P < 0.04). Ovarian IL-2 and IL-4 mRNA were not expressed in either group. There was no significant difference in the expression of IL-8, IL-13, IFN-gamma and TNF-alpha mRNA in the two groups. These findings suggest that abnormal local expression of certain cytokines may contribute to the development of endometriomata.
Mol Hum Reprod 1997 May
PMID:The pattern of cytokine mRNA expression in ovarian endometriomata. 923 23

The interaction of endothelial cells and polymorphonuclear leukocytes (PMNs, neutrophils) is a critical determinant of the acute inflammatory response, and mirrors cell-cell interactions in other biologic systems. Adhesion molecules that tether the two cells together, and signaling factors that bind to receptors on the leukocytes and mediate their spatially-localized activation, govern PMN responses as they adhere to and traverse stimulated endothelial cells. Here we show that cultured human endothelial cells express two members of the C-X-C family of chemokines, epithelial neutrophil activating peptide-78 (ENA-78) and interleukin (IL)-8, when stimulated by IL-1 or certain other agonists. ENA-78, previously thought to be exclusively a product of epithelium, is expressed by in situ endothelium in inflamed human lung and other tissues as well as by cultured endothelial cells. The regulation of ENA-78 and IL-8 share certain features in common and they have overlapping biologic activities, including the ability to induce PMN adhesiveness. This was demonstrated in experiments in which we found that ENA-78 induces inside-out signaling of beta2 integrins on the PMN surface, as does IL-8. Antibody blocking experiments demonstrated that ENA-78 contributes to the proadhesive activity for neutrophils that is released by endothelial cells stimulated with IL-1 for a prolonged period and that it acts in concert with IL-8, which provides the major component of the signal for adhesion under this condition. We also show, however, that the temporal expression and secretion of ENA-78 and other characteristics of its handling by stimulated endothelial cells vary from the expression of IL-8, indicating that differential regulation of the two signaling chemokines occurs in this cell type.
Am J Respir Cell Mol Biol 1997 Aug
PMID:Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion. 927 6

Relatively high concentrations of azathioprine had an inhibitory effect on interleukin 8 (IL-8)- or formyl-methionyl-leucyl-phenylalanine-activated (fMLP)-chemotaxis by human neutrophils. However, application of low concentrations of azathioprine in a concentration gradient gave a chemotactic stimulation to random migration. Stimulation of migration was maximal at a concentration of 5 microM azathioprine; at higher concentrations stimulation decreased again. The activating effect of azathioprine is located in the mercaptopurine moiety of the molecule, since mercaptopurine also stimulated neutrophil migration. In contrast to some other chemotactic agents such as fMLP and IL-8, an activating concentration (5 microM) of azathioprine did not cause an upregulation of CD11b expression on neutrophils in suspension. High concentrations of azathioprine (1 mM) inhibited CD11b expression of fMLP- or IL-8- activated neutrophils; the latter could explain the inhibitory effect of azathioprine. Azathioprine caused a transient stimulation of cGMP level; inhibitors of guanylate cyclase inhibited azathioprine-stimulated migration, suggesting that cGMP was associated with the stimulating effect of azathioprine on migration. Antagonists of cGMP-dependent protein kinase (G-kinase) strongly inhibited azathioprine-activated migration, indicating that the effect of azathioprine proceeds via G-kinase. The antagonists had only a marginal effect on inhibition of IL-8-activated chemotaxis by high concentrations of azathioprine, thus the G-kinase seems not to be of great importance on the inhibitory effect of azathioprine.
Cell Mol Life Sci 1997 Jul
PMID:A cyclic GMP- and G-kinase-dependent effect of azathioprine on migration by human neutrophils. 928 61


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