Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Munro's microabscess of psoriasis has been generally considered to be composed of polymorphonuclear neutrophils (PMNs). However, the cell-components of the microabscess has not been fully clarified. To identify the presence of mononuclear cells (MNCs) in Munro's microabscess and the subcorneal pustule of pustular psoriasis, we observed psoriatic lesions histologically and immunohistologically. Morphologically a few MNCs were found among PMNs and they seemed to include Langerhans cells (CD1a+), helper/inducer T cells (CD4+, CD5+), and macrophages (CD14+) which expressed HLA-DR. Some of them seemed to produce gamma-interferon (IFN-gamma), interleukin 6 (IL-6) and IL-8. The keratinocytes surrounding the microabscess also had IL-8 and some epidermal cells of the proliferated epidermal papillae also expressed IL-6 and IL-8 in psoriatic lesions. The production of IL-6 and IL-8 is considered to effect both chemotaxis and the proliferation of epidermal cells. The presence of these cytokines also suggests that MNCs exist in Munro's microabscess and that they might contribute to the microabscess formation of psoriatic lesions.
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PMID:The cell-components and cytokines in the subcorneal microabscess of psoriasis. 182 82

Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture.
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PMID:Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. 189 27

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.
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PMID:Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. 190 12

T lymphocytes and mononuclear cells preferentially accumulate in the epidermis in inflammatory skin disease. To determine the role of keratinocytes in both the chemotaxis and adhesion of these cells to the epidermis, cultured keratinocytes were incubated with IFN-gamma and tumor necrosis factor-alpha (TNF-alpha), and mRNA detected and quantitated for IL-8, monocyte chemotaxis and activating factor, and intercellular adhesion molecule-1. Whereas induction of these mRNAs was either absent, or relatively weak and transient, to either IFN-gamma or TNF-alpha alone, when administered in combination there was a dramatic increase and persistence in the induction of all three genes. Pretreatment of the keratinocytes with cycloheximide failed to eliminate transcription, implying that all three are primary response genes. Transforming growth factor-beta, which modulates other keratinocyte functions (not related to adhesion or chemotaxis of inflammatory cells) failed to induce any of the genes. These novel findings potentially explain the selective recruitment of T cells and monocytes observed in inflammatory skin disease, because IFN-gamma and TNF-alpha can co-ordinately regulate keratinocyte-derived chemoattractants and adhesion molecule production.
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PMID:Marked synergism between tumor necrosis factor-alpha and interferon-gamma in regulation of keratinocyte-derived adhesion molecules and chemotactic factors. 210 43

In order to identify novel mediators synthesized in activated macrophages, a cDNA library was prepared from cultures of the mouse macrophage cell line RAW 264.7 that had been treated with lymphokine-rich conditioned medium from mitogen-stimulated mouse spleen cells. Differential plaque hybridization identified a cDNA, designated m119, that detected a 1.6-kilobase mRNA that accumulated in response to gamma-interferon (IFN-gamma) but not in response to other macrophage activators, including IFN-alpha, IFN-beta, and lipopolysaccharide. The mRNA encoded a predicted protein of Mr 14,461 containing a 21-amino acid signal peptide. The primary structure of the predicted protein indicated that it is a member of a recently described family of cytokines related to platelet factor 4, including Gro/melanoma growth stimulatory activity and neutrophil-activating peptide/interleukin 8. The selective induction of the m119 mRNA by IFN-gamma that the predicted m119 protein mediates a macrophage activity regulated by IFN-gamma. The m119 protein may be a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory responses. It is proposed that the gene encoding this protein be called mig, for monokine induced by gamma interferon.
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PMID:A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. 211 67

Hyper-IgE syndrome is a rare immunodeficient disorder characterized by recurrent severe staphylococcal infections of the skin and sinopulmonary tract, chronic eczematoid rashes, coarse facial features, mild eosinophilia, and markedly elevated serum IgE levels. Hyperimmunoglobulinemia D, depressed DTH, and varying degrees of pathogenesis of this syndrome is unknown. The clinical manifestations and the recent research findings indicated the followings: 1) increased production of IL-4: hyperimmunoglobulinemia E, increased number of Fc epsilon R(+)-cells in peripheral blood, 2) defective production of IFN-gamma: abnormal local inflammatory responses (formation of cold abscesses), chemotactic defect in the circulating neutrophils (abnormalities in IFN-gamma/IL-8 pathway), depressed DTH, 3) T-cell immunodeficiency?-chronic dermatitis? 4) genetic factors (frequent familial occurrence, characteristic facial appearance with broad nasal bridge). These observations led us to postulate that both the increased production of IL-4 and the defective production of IFN-gamma may be the immunopathological bases of this syndrome. Recently, these cytokines were demonstrated to be secreted by different subsets of helper T-cells, designated TH1 and TH2, in murine system, suggesting that the regulatory imbalances between IL-4 and IFN-gamma in this syndrome might be due to the differential activation or inactivation of these helper T-cell subsets.
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PMID:[Hyper IgE syndrome--a disease of imbalanced activation of helper T-cell subsets?]. 214 8

Previously we have isolated about 60 novel cDNA clones whose corresponding mRNAs are induced by mitogenic activation in human peripheral blood T cells. Here we describe the primary structure and regulation of two such cloned genes, pAT 464 and pAT 744, which may encode new lymphokines/cytokines. Similar to IL-2, both genes require the synergy of agents such as PHA and PMA for optimal expression, and, in addition, the induction of both is sensitive to the immunosuppressive drug cyclosporin A. The two genes can be expressed in T cells, B cells, and the promyelocytic cell line HL60, but they are not expressed in human fibroblasts, suggesting that their expression is restricted to hematopoietic lineages. The predicted peptides encoded by these two clones feature hydrophobic N-terminal leaders characteristic of secreted proteins. The predicted size of both proteins is about 8 kDa upon cleavage of the putative leader peptide. pAT 464 and pAT 744 are very similar to each other and also share some critical amino acid similarity with a newly emerging family of secreted factors including connective tissue activating factor III, platelet factor 4, an IFN-gamma-induced factor, macrophage inflammatory protein, and a factor chemotactic to neutrophils (3-10C, monocyte-derived neutrophil chemotactic factor, neutrophil-activating factor). Some of these factors have been shown to display functions associated with an inflammatory response and/or have mitogenic activities. Collectively, the data presented here suggest that pAT 464 and pAT 744 encode novel lymphokines/cytokines which may play roles during an immune response similar to those enacted by these structurally related factors.
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PMID:Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors. 252 82

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
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PMID:Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. 750 78

We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-beta (8/25 lines) and IFN (7/12), but not IL-2. Immunoassays detected IL-1 alpha (4/25), IL-1 beta (12/25), IL-6 (13/29), IL-8 (29/29), TGF-beta 2 (5/12) and GM-CSF (11/29), but not IL-3, IL-4, TNF-alpha, or IFN-gamma. There was no preferential association of cytokine production with cells cultured from primary versus metastatic disease, and only IL-8 was produced by all lines tested. These data demonstrate that cultured melanomas produce a variety of cytokines which are potentially capable of influencing tumor growth in vivo.
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PMID:Production of multiple cytokines by cultured human melanomas. 751 80

There has been a number of conflicting reports regarding the T lymphocyte chemotactic activities of several cytokines. IL-2 and IFN-gamma are known to promote augmentation of immune inflammation, whereas IL-4, IL-10, and IL-13 display immunomodulatory effects on inflammatory cells including inhibition of cytokine production. Their effects on chemotaxis of inflammatory cells are unknown. We observed that IL-1 alpha could induce chemotaxis both in overnight cultured and anti-CD3 mAb-activated T lymphocytes and that overnight culture and anti-CD3 activation increase the number of IL-1R on T lymphocytes. In contrast, IL-8 selectively attracts freshly isolated T lymphocytes. Staurosporine inhibits freshly isolated T lymphocyte chemotaxis toward IL-8, whereas tyrphostin 23 inhibits chemotaxis of overnight cultured and anti-CD3-activated T lymphocytes toward IL-1 alpha. We have found that IL-2 and IL-13 inhibit the chemotactic migration of both CD4+ and CD8+ T lymphocytes toward IL-8, and RANTES. IL-4 inhibits only CD8+ T lymphocyte chemotaxis toward RANTES, IL-8 and IL-10. IL-10 inhibits only CD4+ T lymphocytes in their chemotactic response toward RANTES and IL-8. IFN-gamma does on the other hand augment the sensitivity of human T lymphocytes to chemotactic stimuli. Thus, our results demonstrate that different proinflammatory cytokines will induce chemotactic migration of T lymphocytes under different circumstances acting through different signaling pathways. The T cell-derived cytokines IL-2, IL-4, IL-10, and IL-13 are able to block further T lymphocyte chemotaxis, thus leading to a focusing of T lymphocytes in an area of T lymphocyte activation. These mechanisms seem relevant in our understanding of the specific and continuous localization of T lymphocytes in allergic and autoimmune disorders.
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PMID:Regulation of human T lymphocyte chemotaxis in vitro by T cell-derived cytokines IL-2, IFN-gamma, IL-4, IL-10, and IL-13. 753 13


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