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)

Endothelial cell (EC) activation plays a key role in inflammation, thrombosis and organ rejection. Normally, EC are in a quiescent state in which their function is to prevent coagulation and thrombosis, and to participate in the regulation of leukocyte migration from the bloodstream into the tissue. Upon activation with cytokines or other stimuli, EC up-regulate a number of genes, including E-selectin (ELAM-1), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, interleukin (IL)-1, IL-8, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), MCP-1 (monocyte chemoattractant protein-1) and endothelial cell inducible gene (ECI-6). Arachidonic acid (AA) is produced by several cell types, including EC, and acts on various cells. We report here that AA inhibits the up-regulation of some, but not all genes that are induced with EC activation in a dose-dependent manner. AA suppresses TNF-alpha, IL-1 alpha, LPS or PMA-induced E-selectin expression, as well as mRNA accumulation of E-selectin, ICAM-1 and IL-8 stimulated by TNF-alpha. The inhibition appears to be at the level of transcription. At the same time under the same conditions AA does not, repress mRNA accumulation for PAI-1, ECI-6, MCP-1 and VCAM-1. We suggest that the induced expression of AA with EC activation may result in a negative feedback loop regulating further activation.
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PMID:Selective suppression of endothelial cell activation by arachidonic acid. 876 41

We examined the effects of interleukin-12 (IL-12) and interleukin-13 (IL-13) on cytokine, cytokine inhibitor and prostaglandin E (PGE) release from synovial fibroblasts and blood mononuclear cells (MNC). In resting synovial fibroblasts, we found that IL-13 is an inhibitor of IL-8 and PGE release. A significant decrease of PGE synthesis caused by IL-13 was also observed in tumor necrosis factor (TNF)-alpha-stimulated synovial fibroblasts, whereas IL-12 had no regulatory effects on these cells. In resting and cytokine-stimulated MNC, IL-13 markedly inhibited IL-1 beta, IL-8 and monocyte chemoattractant protein-1 (MCP-1) release and potently stimulated interleukin-1 receptor antagonist (IL-1ra) synthesis. In contrast, IL-12 stimulated the production of IL-1 beta and MCP-1 in TNF-alpha-stimulated MNC and inhibited IL-1ra synthesis in cytokine-stimulated cells. These findings identify novel biological actions of IL-12 and IL-13 on connective tissue and on blood mononuclear cells which indicate their regulatory functions as enhancer and suppressor of inflammatory processes, respectively.
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PMID:Opposite effects of interleukin-13 and interleukin-12 on the release of inflammatory cytokines, cytokine inhibitors and prostaglandin E from synovial fibroblasts and blood mononuclear cells. 881 67

Chemokines or chemotactic cytokines are small peptide molecules involved in the recruitment of leukocytes to sites of infection. This article reviews recent research investigating the interaction between chemokines and viral infection. There is considerable evidence from cellular studies showing that both respiratory epithelium and recruited neutrophils contribute to the chemokine response in paramyxovirus infection. We have shown that plasma concentrations of IL8, a neutrophil and T-cell chemoattractant, are elevated in patients with respiratory syncytial virus infection compared to controls (p < 0.03). In retroviral infection such as that caused by HIV, monocytes and macrophages are the principal source of chemokines involved in recruitment of antiviral leukocytes. Secretion of certain chemokines such as monocyte chemoattractant protein-1, during the immune response to infection, may be dysregulated by concomitant HIV infection, and such effects may be due to actions of specific controlling elements in the viral genome such as the tat region. Herpesviruses adopt a different strategy of expressing chemokine receptors to either utilize or subvert the host chemokine response. Thus, there are diverse and complex interactions involving chemokines and viral infection which we are only just beginning to dissect.
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PMID:Chemokines in viral disease. 890 32

Endometrial leukocyte subpopulations vary over the reproductive cycle, but no data exist on the mechanism regulating their recruitment into uterine tissue. This study has evaluated the role of progesterone in the recruitment of selected leukocyte populations in early pregnancy decidua. Decidua was collected from women in early pregnancy at the time of vacuum aspiration of the uterus 6, 12, 24 and 36 h after taking 200 mg mifepristone (RU486). Standard immunohistochemical techniques were employed to demonstrate the selected leukocyte populations in decidual tissue and these were analysed using imaged analysis. Fresh decidua was incubated in medium for 24 h and supernatants assayed for interleukin (IL-8) (neutrophil chemotactic factor) and MCP-1 (monocyte chemoattractant protein-1) content. Analysis of variance demonstrated a significant increase in tissue monocyte number in decidua 12-36 h after mifepristone administration. No significant changes in other leukocyte subpopulations were observed. Decidua IL-8 concentrations were significantly increased (P = 0.019) 6 h after mifepristone and decidual MCP-1 concentration rose (non-significant) and fell significantly (P = 0.029) between 6 and 12 h after mifepristone. Progesterone withdrawal may initiate a local cascade of events involving inflammatory mediators which in turn are responsible for the influx of monocytes. This influx may be essential in the process of shedding of endometrium or decidua since monocytes and neutrophils are important sources of proteases and collagenases. Furthermore, these cells are potential local sources of immunomodulatory cytokines.
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PMID:Sex steroid regulation of leukocyte traffic in human decidua. 894 39

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.
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PMID:Plasma levels of the monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 are elevated in patients with acute myocardial infarction. 904 55

Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell adhesion molecules and cytokines. The latter include chemotactically active cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation. In this study we evaluated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines. HDMECs and an immortalized human dermal microvascular endothelial cell line, HMEC-1, were investigated for the expression of C-X-C and C-C chemokines at mRNA and protein levels. Upon stimulation with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), both HDMECs and HMEC-1 expressed high levels of IL-8, GRO, and monocyte chemoattractant protein-1 (MCP-1). RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines. The C-X-C chemokine IFN-inducible protein-10 was upregulated by IFN-gamma but not by other cytokines studied. Macrophage inflammatory protein-1alpha and beta, 1-309, and ENA-78 could not be induced. The chemokine repertoires of HDMECs and HMEC-1 were compared to those of human umbilical vein endothelium and found to be rather similar with the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs contribute to the dermal cytokine network by selective production of MCP-1, IL-8, GRO, RANTES, and IP-10, which may critically influence the site-specific recruitment of leukocyte subsets.
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PMID:The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines. 907 72

Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is a systemic infection with preponderance for the skin, joints, heart, and nervous system. Inflammatory lesions of target organs are characterized by the presence of spirochetes and inflammatory leukocytes. We have analyzed the potential of B. burgdorferi to induce gene expression of chemokines and adhesion molecules in human endothelial cells, keratinocytes, and fibroblasts. We find induction of the chemokines RANTES (regulated upon activation, normal T cells expressed and secreted), monocyte chemoattractant protein-1, IL-8, gro-alpha, IFN-inducible protein-10, and mig (monokine induced by gamma-IFN), and of the adhesion molecules E-selectin, ICAM-1, and VCAM-1 in endothelial cells and induction of the same chemokines and ICAM-1 in fibroblasts. This is mediated by the lipid moiety of the outer surface lipoprotein A. Induction of chemokine and adhesion molecule genes by B. burgdorferi occurs rapidly and does not require new protein synthesis. Induction is blocked by inhibitors of nuclear factor (NF)-kappa B. We also find that B. burgdorferi induces nuclear translocation of NF-kappa B and a transient increase in the expression of its inhibitor I kappa B-alpha. These findings indicate that B. burgdorferi is a potent inducer of molecules required for leukocyte recruitment to inflammatory foci, and the data suggest that this biologic activity is due to the ability of the spirochetes to activate the pleiotropic transcription factor NF-kappa B.
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PMID:Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts. 912 Feb 85

The endometrium contains a resident population of leukocytes, the number and subtype of which vary throughout the menstrual cycle and in early pregnancy. Factors controlling these fluctuations are unknown, but a combination of proliferation in situ and migration from the vasculature has been proposed. Locally acting inflammatory mediators, including specific chemokines and prostaglandins, have been implicated in these processes. Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are potent chemoattractants and activators for neutrophils and monocytes respectively. Locally acting prostaglandins modulate vascular permeability, and a synergistic action of prostaglandin E (PGE) with IL-8 has been described. In the present study IL-8, MCP-1 and cyclooxygenase-2 (COX-2), the inducible isoform of prostaglandin synthase, were all localized in the endometrium by immunohistochemistry throughout the menstrual cycle and in early pregnancy. All three inflammatory mediators were localized to the perivascular cells of blood vessels in endometrium and decidua, and additional immunoreactivity for COX-2 was identified in the glandular epithelium. The intensity of immunostaining was reduced in the periovulatory, early and mid-secretory phases and significantly increased premenstrually. These results further support the hypothesis that there is a premenstrual migration of leukocytes into the endometrium mediated by chemokines.
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PMID:Chemokine and cyclooxygenase-2 expression in human endometrium coincides with leukocyte accumulation. 922 21

Despite the fact that Helicobacter pylori is known to be non-invasive, mucosal infiltration of inflammatory cells have been observed in the gastric mucosa. The exact pathogenesis of such an inflammatory reaction has not been well defined. We explored the repertoire of cytokine genes expressed in human gastric epithelial cells in response to coculture with H. pylori. After gastric epithelial cells, SNU-5 and KATO III, were infected with H. pylori, expression of several cytokine genes was assessed using quantitative reverse transcription polymerase chain reaction. Interleukin (IL)-8, -1 alpha and -1 beta mRNA were expressed in both gastric epithelial cells throughout the entire infection period. In SNU-5, IL-1 alpha and IL-8 mRNA were expressed at 1 h, reached a peak level at 4 h and then decreased. Interleukin-1 beta mRNA was expressed less frequently than IL-1 alpha, or IL-8 mRNA. In SNU-5 cells, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-alpha) mRNA were expressed at 9 h, but was not expressed in KATO III. Gene expression paralleled the amount of IL-8 protein measured by enzyme-linked immunoabsorbent assay (ELISA). Interleukin-8 mRNA expression was not observed in KATO III cells infected with Campylobacter fetus ssp. fetus, Campylobacter jejuni or Escherichia coli. IL-8 mRNA expression was increased not only in gastric epithelial cells but also in non-gastric cells infected with H. pylori. These results suggest that an inflammatory reaction induced by H. pylori may be initially triggered by an array of pro-inflammatory cytokines expressed by infected gastric epithelial cells.
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PMID:Helicobacter pylori induces an array of pro-inflammatory cytokines in human gastric epithelial cells: quantification of mRNA for interleukin-8, -1 alpha/beta, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1 and tumour necrosis factor-alpha. 925 36

The mechanisms of glomerular damage in IgA nephropathy remain undefined. Mesangial cells (MC) possess Fc receptors for IgA (Fc alpha R), and their occupancy triggers cytokine expression, cell proliferation, and extracellular matrix synthesis. In cultured human MC we examined the effects of soluble IgA aggregates (AIgA) on the activation of nuclear factor-kappa B (NF-kappa B) and the production of proinflammatory chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8, and IFN-inducible protein-10 (IP-10). The exposure of MC to AIgA rapidly activated a NF-kappa B complex constituted of p50 and p65 subunits. NF-kappa B activation was dose dependent, abolished by preincubation with IgA Fc fragments (indicating that AIgA effects occur via specific Fc alpha R), and attenuated by kinase inhibitors. MC stimulation with AIgA increased the mRNA expression of MCP-1, IL-8, and IP-10 in a time- and dose-dependent manner. Maximal expression of IL-8 was observed at 3 h (4.5-fold), while IP-10 and MCP-1 peaked at 6 h (5-fold for both). AIgA also induced biosynthesis and release of the chemokines, which presented biological activity in neutrophil and monocyte chemoattractant assays, peaking at 6 and 9 h, respectively. MC pretreatment with the antioxidant pyrrolidine dithiocarbamate inhibited NF-kappa B activation and chemokine mRNA expression. This study shows that stimulation of Fc alphaR in MC induces gene expression of MCP-1, IL-8, and IP-10, a process partially mediated by NF-kappa B activation. These data may be of importance for a better understanding of the pathogenesis of glomerular damage in IgA immune complex-related diseases.
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PMID:Interaction of IgA with Fc alpha receptors of human mesangial cells activates transcription factor nuclear factor-kappa B and induces expression and synthesis of monocyte chemoattractant protein-1, IL-8, and IFN-inducible protein 10. 931 46


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