UNIPROT:P10145 - FACTA Search

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)

Eosinophilia is a feature of nasal polyposis. The aim of this study was to determine the role of cytokines and allergen in maintaining the eosinophilic infiltrate in this condition. Polyp fragments from house dust mite (HDM)-sensitive atopic individuals and nonatopic individuals were cultured in the presence of HDM, or phytohaemagglutinin (PHA) or culture medium alone. Culture supernatants were assayed for interleukins (IL) 3, 5, and 8 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil survival enhancing activity (ESEA) in vitro. Significant ESEA was produced spontaneously. When polyp tissue from atopics, but not from nonatopics, was stimulated with allergen for 2 days there was a further increase in ESEA associated with a median 12 and fourfold increase in IL-8 and GM-CSF, respectively. This increased ESEA was markedly reduced with anti-GM-CSF and, to a lesser extent, anti-IL-8 blocking antibodies. When stimulated with PHA, polyp tissue from atopic subjects also produced increased ESEA, implicating possible T-cell involvement. This was associated with a small (twofold), but significant, increase in IL-8 and a less consistent increase in GM-CSF. However, anti-IL-8 or anti-GM-CSF blocking antibodies failed to reduce the ESEA in these supernatants, suggesting involvement of other mechanisms. This study suggests that in sensitized individuals, allergen may contribute to polyp eosinophilia by stimulating the production of granulocyte/macrophage colony stimulating factor and interleukin 8.
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PMID:Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from atopic subjects prolongs eosinophil survival. 923 Feb 33

The cytokine interleukin 8 (IL-8) has been shown to be a potent mediator of leukocyte recruitment and neovascularization in inflammatory and neoplastic diseases. In this study we hypothesize that IL-8 produced in the nasal polyp microenvironment is responsible for the leukocyte recruitment seen in nasal polyposis. To test this hypothesis we evaluated nasal polyps for distribution and content of IL-8 antigen with immunohistochemical techniques and radioimmunoassay to determine tissue levels of IL-8. The immunohistochemical results demonstrated that IL-8 antigen staining occurred predominantly within inflammatory cells and epithelium. IL-8 was detected in all nasal polyp tissue homogenates (a mean value of 1767 +/- 1633 pg/mg total protein (TP) with a range of 134 to 3668 pg/mg TP vs control specimens with a mean value of 77 pg/mg TP with a range of 0.09 to 255 pg/mg TP). These data demonstrate the presence and distribution and levels of IL-8 antigen in nasal polyps in vivo, supporting our hypothesis that local production of IL-8 could be an important factor in the sustained recruitment of leukocytes in nasal polyposis. Thus IL-8 likely plays a significant role in the pathogenesis of this disease process and therefore is a potential target for therapeutic intervention.
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PMID:Interleukin-8 expression in human nasal polyps. 937 80

Apart from ventilatory and bacteriologic aspects, understanding the pathomechanisms of inflammation in chronic sinusitis and nasal polyposis seems crucial for further success in disease treatment. New insights into inflammatory processes became recently possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases. The proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and especially the neutrophil-chemoattractant IL-8 play a dominant role in acute sinusitis, as was shown before for viral and allergic rhinitis. In contrast, IL-3 protein dominates the cytokine profile in chronic sinusitis, giving support to a variety of inflammatory cells. The most striking finding was the increased synthesis of IL-5 protein in bilateral nasal polyposis, whereas IL-5 was not found in controls or antrochoanal polyps. As this cytokine is known to enhance eosinophil activation and survival, our data point to IL-5 as a key protein in the pathomechanism of tissue eosinophilia in nasal polyposis. The investigation of cytokine patterns may furthermore help to differentiate between sinusitis subgroups, e.g. in the classification of sinus diseases.
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PMID:Inflammatory mechanisms in chronic sinusitis. 944 69

Nasal fibroblasts play an important role in both nasal polyposis and nasal allergic diseases and they are known to release a number of proinflammatory cytokines, including GM-CSF, IL-8 and IL-6. The aim of this present work was to investigate whether cytokine-stimulated nasal fibroblasts release biologically active RANTES as well as to study the effect of corticosteroids on the ability of nasal fibroblasts to produce the cytokine. Measurements of RANTES by ELISA demonstrated that RANTES is constitutively secreted spontaneously (21+/-4 vs. 19+/-6 ng/ml, respectively p>0.05). Stimulation of these cells with either TNF-alpha, IL-1beta or IFN-gamma induce further release of RANTES in a dose-dependent manner with TNF-alpha being the most potent stimulus. RANTES mRNA expression in nasal fibroblasts correlated with the amount of protein released in the culture supernatant upon cytokine stimulation. Moreover, chemotaxis studies demonstrated that the nasal-derived RANTES was biologically active on eosinophils. Betamethasone and hydrocortisone were found to downregulate RANTES mRNA expression in TNF-alpha-stimulated fibroblasts. These observations suggest that RANTES released by nasal fibroblasts may regulate eosinophil recruitment in nasal disease while glucocorticoids may inhibit the influx of these cells by suppressing the production of RANTES.
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PMID:RANTES production by cytokine-stimulated nasal fibroblasts: its inhibition by glucocorticoids. 975 49

Cytokines are potent biologic factors involved in the regulation of inflammation, immune defense, and wound healing. Recently, growing interest has developed in the role of cytokines in chronic sinusitis and nasal polyposis. In the present study, we investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a specific form of rhinosinusitis is associated with the expression of a certain cytokine profile. Sinus mucosa from patients with acute sinusitis (n = 10), chronic sinusitis (n = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8) and controls of turbinate mucosa (n = 7) were sampled. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF, interferon-gamma) of tissue homogenates was measured using ELISA technique. In acute sinusitis, the synthesis of proinflammatory cytokines and of the neutrophil chemokine IL-8 and IL-3 appeared to be upregulated. Chronic sinusitis mucosa demonstrated no significantly increased concentrations of the measured cytokines. In bilateral nasal polyposis, but not in antrochoanal polyps, the eosinophil related cytokine IL-5 was strongly upregulated. From these findings, it appears that specific cytokine patterns are found in different forms of sinusitis, and that IL-5 may represent the most important cytokine responsible for tissue eosinophilia in nasal polyposis.
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PMID:Cytokines in nasal polyposis, acute and chronic sinusitis. 988 92

Nasal polyposis is an inflammatory condition of the nose and the sinuses characterised by a marked infiltration of eosinophils in addition to lymphocytes, mast cells and macrophages. The selective recruitment of eosinophils to inflammatory sites is mediated by CC chemokines such as Eotaxin and Eotaxin-2. In the present study histology, immunohistochemistry and ELISA were performed. The levels of Eotaxin and Eotaxin-2 and for comparison other chemokines RANTES and IL-8 were measured in nasal polyp tissue and in control nasal tissue. On histological examination 6 polyps showed an oedematous structure, one was glandular and one had a fibromatous pattern, while all showed a marked eosinophil infiltration. Immunohistochemistry of the polyps showed that epithelial cells were strongly positive for Eotaxin and IL-8, whereas endothelial cells stained positive for Eotaxin-2. Significantly higher amounts of Eotaxin, Eotaxin-2 and IL-8 were detected in polyp tissue when compared with control middle turbinates. The increased levels of eosinophil-stimulating chemokines, such as Eotaxin and Eotaxin-2 in nasal polyps suggest that they may be important regulators of eosinophil recruitment in this inflammatory disease.
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PMID:[The role of chemokines in nasal polyps]. 1114 53

Chemokines are attractants and regulators of cell activation. Several CXC family chemokine members induce angiogenesis and promote tumor growth. In contrast, the only CC chemokine, reported to play a direct role in angiogenesis is monocyte-chemotactic protein-1. Here we report that another CC chemokine, eotaxin (also known as CCL11), also induced chemotaxis of human microvascular endothelial cells. CCL11-induced chemotactic responses were comparable with those induced by monocyte-chemotactic protein-1 (CCL2), but lower than those induced by stroma-derived factor-1alpha (CXCL12) and IL-8 (CXCL8). The chemotactic activity was consistent with the expression of CCR3, the receptor for CCL11, on human microvascular endothelial cells and was inhibited by mAbs to either human CCL11 or human CCR3. CCL11 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and Matrigel plug assays. The angiogenic response induced by CCL11 was about one-half of that induced by basic fibroblast factor, and it was accompanied by an inflammatory infiltrate, which consisted predominantly of eosinophils. Because the rat aortic sprouting assay, which is not infiltrated by eosinophils, yielded a positive response to CCL11, this angiogenic response appears to be direct and is not mediated by eosinophil products. This suggests that CCL11 may contribute to angiogenesis in conditions characterized by increased CCL11 production and eosinophil infiltration such as Hodgkin's lymphoma, nasal polyposis, endometriosis, and allergic diathesis.
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PMID:Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. 1139 May 13

Accumulated experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in the mechanism of furosemide diuretic action. It was reported that the drug is highly bound in the adrenals, lungs, kidney, spleen, and liver. In patients with liver cirrhosis, furosemide exerted a markedly decreased natriuretic effect compared with normal subjects, and the plasma levels of circulating endothelin and atrial natriuretic factor (ANF) were significantly elevated. In neonates, after administration of furosemide, the urinary excretion of endothelin-1 and aldosterone increased markedly, and it is known that endothelin may release ANF and aldosterone in a dose-dependent manner. Furosemide was used to stimulate zona glomerulosa, whereas ANF decreased the production of steroids in zona glomerulosa and fasciculata cell culture owing to stimulation by various factors. Because the concomitant use of ANF and furosemide appeared to be diuretically effective in newborns after cardiac surgery, one may suggest that furosemide competes with ANF for its effects on the adrenals. Furosemide administered by inhalation exerted a protective effect on allergic and perennial nonallergic rhinitis and was effective in preventing the postsurgical recurrence of nasal polyposis. The drug can also be used as an antiasthmatic agent. In preterm ventilator-dependent infants with chronic lung disease, aerosolized furosemide improved pulmonary function with no marked effect on diuresis. In adults and children with asthma, furosemide exerted a protective effect against bronchoconstriction induced by several indirect stimuli similar to that of disodium cromoglycate or nedocromil. Aerosolized furosemide had a preventive effect also on bronchoconstriction induced by inhaled lysine acetylsalicylate in patients with aspirin-sensitive asthma. In high-dose beclomethasone-dependent asthma, inhaled lysine acetylsalicylate and furosemide exerted a mutually potentiating antiasthmatic activity, allowing considerable sparing of the inhaled steroid. It is proposed that this effect may be explained by the corticosteroid-sparing action of lysine released from the lysine acetylsalicylate molecule because similar beneficial effects were also obtained after the concomitant use of epsilon-aminocaproic acid (whose chemical structure is almost the same as that of lysine) and prednisone. Furosemide exhibited an anti-inflammatory effect through inhibition of production and release of cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha from peripheral mononuclear cells, which may have a beneficial effect on local inflamed tissue imbalance in the ratio of different cytokines, thus improving the sensitivity of target cells to endogenous glucocorticosteroids.
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PMID:Furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases. 1211 21

Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 microg.day(-1)). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.
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PMID:Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps. 1545 38

Nasal polyps are characterized by eosinophilic infiltration and presence of inflammatory mediators, such as total IgE, eosinophil cationic protein (ECP) and cytokines. The role of atopy in nasal polyp pathogenesis is still unclear. Therefore, we evaluated serum IgE levels, nasal mucus concentrations of ECP and cytokines and the number of infiltrating eosinophils in nasal tissue of polyps from atopic and non-atopic patients. Samples were obtained from a randomized population of 31 patients with nasal polyposis having endonasal sinus surgery and of 13 control subjects undergone corrective surgery of the nasal septum. On the basis of medical history of allergy, positive skin-prick tests and total IgE levels, patients with polyposis were divided in atopic (n = 13) and non-atopic (n = 18) patients. We determined levels of IgE in blood, ECP and cytokines (IL-4, IL-6, IL-8, IFN-gamma and IL-2) in nasal mucus, and number of infiltrating eosinophils in nasal tissue. The concentrations of total IgE, ECP, IL-4 and IL-8 and eosinophilia were significantly higher in all patients with nasal polyps compared with controls. Inside, all patients with nasal polyposis showed lower levels of IL-6, IFN-gamma and IL-2 compared with controls. The atopic patients showed significant differences when compared with non-atopic patients for the higher concentrations of total IgE (698.80+/-322.24 vs. 279.63+/-234.11; P < 0.0001) and IL-8 (1437.2 pg/ml+/-1250.7 vs. 605.5 pg/ml+/-481.1; P < 0.015). These findings suggest that inflammation still remains the major factor in the etiology of nasal polyposis and show different levels of inflammatory mediators into atopic and non-atopic patients.
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PMID:Inflammatory mediators and eosinophilia in atopic and non-atopic patients with nasal polyposis. 1593 9

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