UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-8 (IL-8) is an 8 kD chemokine and angiogenic factor produced by alveolar macrophages, endothelial cells, monocytes, fibroblasts, T lymphocytes, and epithelial cells in response to a variety of stimuli, including LPS, TNF-alpha, IL-1, IL-7, and hypoxia. Pulmonary tumors produce a variety of growth factors and cytokines that may act in both autocrine and paracrine fashion. A549, a well-characterized human lung adenocarcinoma line, was cloned for different levels of IL-8 production by limiting dilution. Clone 3B4 produced 361 +/- 73 pg/ml, and clone 2B2 produced 7818 +/- 614 pg/ml of IL-8 (p = 0.003). Clone 3B4 proliferated at 1.7 times the rate of 2B2. Anti-IL-8 reversed the decrement in proliferation of clone 2B2 by 50%, but recombinant IL-8 decreased the proliferation of 3B4 by 40-55% compared with control. In addition to A549, three other non-small cell lung cancer (NSCLC) lines showed significantly decreased proliferation in response to exogenous recombinant IL-8 (5-30 ng/ml; p < 0.05). These findings suggest that in addition to its chemotactic and angiogenic activities, IL-8 may inhibit lung tumor proliferation by both autocrine and paracrine pathways.
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PMID:Interleukin-8 inhibits non-small cell lung cancer proliferation: a possible role for regulation of tumor growth by autocrine and paracrine pathways. 864 Apr 52

The expression of cytokine transcripts has been investigated in a series of cultured human meningiomas using reverse transcriptase linked polymerase chain reaction (RT-PCR), which allowed simultaneous analysis of a range of cytokines. The main histological subgroups of meningioma were investigated; these included transitional, fibroblastic, and syncytial as well as atypical meningiomas. Meningiomas from each of the different histological subgroups were subjected to a standard tissue culture regime. Total RNA was extracted from representative cultures and reverse-transcribed to yield cDNA. PCR was performed using oligonucleotide primers designed to detect interleukin (IL)-1 alpha/beta to IL-8, transforming growth factor (TGF)beta 1-3, tumour necrosis factor (TNF)alpha/beta, and interferon (IFN)gamma. Transcripts for IL-3, IL-6, IL-8, and TGF beta 3 were detected in all cultures. Transcripts for the three isomers of TGF beta were expressed in the transitional and fibroblastic meningioma cells. TGF beta 2 and TGF beta 3 transcripts were expressed in the syncytial and TGF beta 1 and TGF beta 3 in the atypical meningioma cells. IL-1 beta transcripts were expressed in fibroblastic and atypical cultures and TNF beta transcripts were expressed in syncytial and transitional cultures only. Transcripts for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF alpha, or IFN gamma were not detected in any of the meningioma cultures. This investigation using cells cultured from a small number of tumours from each of the classic histological subtypes suggests that there is a distinct pattern of cytokine mRNA expression linked with histological classification.
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PMID:RT-PCR detection of cytokine transcripts in a series of cultured human meningiomas. 912 Jul 36

Human peripheral blood leukocytes (hPBL) are a rich source of natural leukocyte interferon (IFN-alpha) when treated with Sendai virus. Sendai virus treatment of hPBL will also result in significant production of several chemokines and cytokines such as macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8, in a time-dependent way. A significant amount of MCP-1 is constitutively produced in overnight culture of leukocytes. The most abundant cytokine is IFN-alpha, which is induced to its maximum level approximately 11-15 h after addition of Sendai virus. The amount of IFN-alpha induced at 15 h after Sendai virus treatment is more than 16-fold higher than those of MIP-1alpha, MIP-1beta, and RANTES. IFN-alpha is also induced more than 60-fold higher than TNF-alpha and IL-8. The amount of IL-6 induced is approximately 400-fold less than IFN-alpha. Limited amounts of other cytokines such as IL-1alpha, IL-1beta, macrophage colony-stimulating factor, TNF-beta, and IFN-gamma are also induced in Sendai virus-treated hPBL. No measurable amount of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, leukemia inhibitory factor, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-11, or IL-12 was induced in the supernatant of Sendai virus-treated hPBL.
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PMID:Cytokines induced by Sendai virus in human peripheral blood leukocytes. 869 16

Human fetal thymic epithelial cells (TEC) were cultured under serum-free conditions. The TEC were analyzed for the secretion of 14C-labelled peptides and of IL-3, IL-6 IL-7, IL-8, GM-CSF, LIF, fibronectin and thymosin alpha 1 by ELISA tests. IL-3 and IL-7 were not detected from these TEC. Lack of IL-7 and presence of thymosin alpha 1 and of the surface molecule TE-4 depicts these cells as subcapsular/medullary TEC. TEC secreted constitutively IL-6, IL-8, fibronectin and thymosin alpha 1 but not GM-CSF of LIF. Stimulants included recombinant IL-1 and monoclonal antibodies to the surface adhesion molecules ICAM-1 and LAF-3. In addition, hydrocortisone (2.7 x 10(-7) M) was used to dissect secretion patterns. Recombinant IL-1, anti ICAM-1, and anti LFA-3 alone and collectively induced modest but significant increases in the secretions of 14C-labelled peptides and of IL-6 and IL-8 which were not inhibited by HC. Recombinant IL-1 but not anti ICAM-1 and anti LFA-3 induced GM-CSF and LIF. HC inhibited the secretion of GM-CSF and LIF induced by IL-1. None of the stimulants augmented the constitutive secretion of fibronectin or thymosin alpha 1 and HC inhibited thymosin alpha 1 secretion. TEC secretion of cytokines but not thymosin alpha 1 and fibronectin appear to be regulated in a more complex manner than heretofore recognized.
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PMID:IL-1, ICAM-1, LFA-3, and hydrocortisone differentially regulate cytokine secretion by human fetal thymic epithelial cells. 872 54

Expression of IL-2R was examined on human fibroblasts isolated from different tissues. By specific binding assay it is shown that [125I]IL-2 bound to subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The presence of binding sites for IL-2 was also confirmed by immunofluorescence and flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25), p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and protein level. Although addition of IL-2 to fibroblast cultures did not significantly alter growth kinetics of these cells, the IL-2R complex displayed by fibroblasts appeared to be functional in that addition of IL-2 to these cells led to enhanced expression of the JE gene coding for the monocyte chemoattractant protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2 appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL-7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These observations suggest that the range of cellular targets of IL-2 is broader than originally appreciated. IL-2 may thus serve to integrate fibroblasts and monocytes into a coordinated response of the connective tissue initiated by T lymphocytes.
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PMID:Human fibroblasts express functional IL-2 receptors formed by the IL-2R alpha- and beta-chain subunits: association of IL-2 binding with secretion of the monocyte chemoattractant protein-1. 875 38

We have recently demonstrated that the combination of IL-2 and IL-4 blunts T cell responses to glucocorticoids in steroid resistant (SR) asthma by reducing glucocorticoid receptor (GCR)-binding affinity. Since immune activation appears to be involved in the acquisition of steroid resistance, we sought to identify whether other cytokines could also induce diminished GCR-binding affinity. In the current report, utilizing a [3H]dexamethasone radioligand-binding assay and Scatchard analysis, we found that IL-13, a cytokine with similar actions as IL-4, could induce diminished GCR binding-affinity (GCR Kd = 34.4 +/- 2.3 nM with IL-13 vs Kd = 8.8 +/- 0.7 nM for unstimulated control cells; p < 0.001) in PBMC from normal subjects. In contrast, PBMC incubated with IL-1, IL-3, IL-5, IL-7, IL-8, IL-12, or granulocyte-macrophage-CSF had no effect on GCR-binding affinity; and no additive effect to the decreased GCR-binding affinity was noted when IL-13 was cocultured with IL-2 or IL-4. The cell target of IL-13-induced GCR effects was studied and found to reside in the non-T cell population; specifically, the monocyte fraction. To determine the functional significance of the decreased GCR-binding affinity, monocytes were pretreated with and without IL-1 3 prior to stimulation with LPS and hydrocortisone. IL-13 pretreatment of monocytes significantly diminished (p = 0.005) the suppressive effects of hydrocortisone on LPS-induced IL-6 production. IL-13, by virtue of its ability to induce diminished GCR-binding affinity, may contribute to impaired GC responsiveness during inflammatory illnesses.
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PMID:A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. 880 70

Articular chondrocytes from nine arthritic patients, five infants, and Balb/c neonatal mice were analyzed for the presence of various cytokine mRNAs by a reverse transcriptase polymerase chain reaction (RT-PCR). Four cytokine mRNAs, interleukin (IL)-6, IL-8, IL-11, and macrophage colony stimulating factor (M-CSF), were detected in all human chondrocytes, regardless of source. IL-10, IL-12p35, and tumor necrosis factor alpha (TNF-alpha) transcripts were found in at least 12 of the 14 human samples. IL-13, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and TNF-beta mRNAs were found more predominantly in infant samples and in samples from patients with rheumatoid arthritis (RA) compared with samples from patients with osteoarthritis (OA). Another group of cytokine mRNAs, IL-1 (alpha, beta), IL-4, IL-5, and IL-7, were only weakly expressed in some human samples. The cytokine transcripts that were not found were IL-2, IL3, and interferon gamma (IFN-gamma). Because of the large array of cytokine transcripts detected, human chondrocyte preparations were further purified by reacting them with a monoclonal antibody specific to chondrocyte differentiation antigen and subjecting them to fluorescent-activated cell sorting. A similar array of cytokines was found between the sorted and unsorted chondrocytes, although TNF-alpha, G-CSF and GM-CSF transcripts appeared to be upregulated during the sorting process. Human chondrocytes that dedifferentiated into fibroblasts (a 40-day and a 77-day culture) no longer expressed mRNAs for IL-1, G-CSF, GM-CSF, and TNF-alpha, but all other cytokine mRNAs remained detectable. Although certain phenotypic characteristics were lost, including reactivity to chondrocyte-specific monoclonal antibodies and morphological features, chondrocytes in long-term culture still expressed cytokine mRNAs. As expected, more consistent results were obtained when seven preparations of chondrocytes from neonatal Balb/c mice were examined using available cytokine primers. They contained IL-1, IL-5, IL-6, IL-7, IL-12, GM-CSF, M-CSF, transforming growth factor beta (TGF-beta), TNF-alpha, and TNF-beta mRNAs but lacked IL-2, IL-3, IL-4, IL-10, and IFN-gamma mRNAs. Future experiments to define conditions by which these cytokine protein products are expressed are needed to help assess their roles in chondrocyte biology and in disease states.
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PMID:Cytokine mRNA repertoire of articular chondrocytes from arthritic patients, infants, and neonatal mice. 885 28

Vascular endothelial cell addressins play an important role in lymphocyte homing in secondary lymphoid organs and in chronic inflammatory areas. A SV40 large T antigen-immortalized cell line from peripheral lymph nodes, HECa1O [Bizouarne et al., 1993a], was used to characterize the location of addressins with regard to environmental factors and cytokines. For this purpose, two monoclonal antibodies, MECA 79 and MECA 367, specific for peripheral lymph node vascular addressin and for mucosal addressin (Peyer's patches), respectively, were bound to unstimulated HECa1O cells. Both mucosal and peripheral addressins were detected inside the cells and in cellular extracts of the resting cells. On the cell surface, both addressins could be evidenced on the same cells at a moderate level of expression. They partly mediate the EL4/EL4IL2 lymphoma cells' adhesion to HECa1O cells. Supernatants of cultured peripheral lymph node or Peyers' patch cells induced expression of MECA 79 or MECA 367 antigens, respectively, on the surface of HECa1O cells. Interleukins, IL-7, IL-3, and IL-8, induced the cell-surface appearance of MECA 79 but not of MECA 367 antigen. Therefore, the same cell type synthesizes both antigens, but the expression of these antigens on the cell surface is independently regulated, thus uncovering a characteristic tissue type-specific as well as environment-sensitive properties of microvascular endothelial cells.
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PMID:Selective induction of peripheral and mucosal endothelial cell addressins with peripheral lymph nodes and Peyer's patch cell-conditioned media. 897 77

The interleukin-12 receptor (IL-12R)beta1 chain is an essential component of the functional IL-12R on both human T and natural killer cells. In this report it is shown that activation of human peripheral blood mononuclear cells (PBMC) with anti-CD3 monoclonal antibody (mAb) or phytohemagglutinin resulted in the up-regulation of IL-12Rbeta1 expression and IL-12 binding. Kinetic studies revealed that maximum expression of IL-12Rbeta1 and IL-12 binding occurred on days 3-4. Anti-CD3-induced expression of IL-12Rbeta1 chain and IL-12 binding by PBMC was augmented by anti-CD28 mAb, indicating that the potentiating effect of anti-CD28 on T cell responses to IL-12 could be mediated, at least in part, by the enhancement of IL-12R expression. Among 16 cytokines tested, IL-2, IL-7 and IL-15 markedly induced IL-12Rbeta1 expression and IL-12 binding on resting PBMC, whereas IL-1alpha and tumor necrosis factor-alpha had a minimal enhancing effect. In contrast, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-alpha, IFN-gamma, granulocyte/macrophage colony-stimulating factor and transforming growth factor (TGF)-beta2 had no detectable enhancing effect. Anti-CD3-induced expression of IL-12Rbeta1 and of low-affinity IL-12 binding sites was partially inhibited by TGF-beta2, IL-10 and IL-4; however, TGF-beta2 and IL-10 completely abolished anti-CD3-induced expression of high-affinity IL-12 binding sites. Consistent with the reduction of high affinity IL-12 binding sites, PBMC activated with anti-CD3 mAb in the presence of TGF-beta2 or IL-10 failed to produce IFN-gamma or to proliferate in response to IL-12. These results suggest that Th2 cell-derived cytokines can inhibit IL-12-induced biological functions by inhibiting IL-12R expression and that expression of a second subunit of the IL-12R (IL-12Rbeta2), required for the formation of high-affinity IL-12 binding sites, may be more highly regulated by TGF-beta2 and IL-10 than is expression of IL-12Rbeta1.
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PMID:Regulation of interleukin-12 receptor beta1 chain expression and interleukin-12 binding by human peripheral blood mononuclear cells. 902 11

We studied the effects of serine proteases on cytokine gene expression by cultured normal human keratinocytes. In resting keratinocytes, steady-state mRNA levels for interleukins IL-1 alpha, IL-1 beta, IL-7, and IL-8, transforming growth factors alpha and beta, and tumor necrosis alpha were sufficient to be detected by our reverse transcriptase-polymerase clozin reaction method. Incubation of keratinocytes with 25 nM trypsin or 1 unit/ml thrombin for 24 hr selectively upregulated mRNA levels for granulocyte-macrophage colony-stimulating factor (GM-CSF) and Il-6 to detectable levels. Keratinocytes secreted GM-CSF and IL-6 protein in response to these proteases. Monensin did not inhibit the gene expression for the cytokines, thereby excluding the possibility of intervention by secreted molecules. Aprotinin and argatroban inhibited the effects of the proteases. SFLLRN and SLIGRL, tethered ligand receptor peptides for thrombin receptor and for proteinase-activated receptor 2 (PAR-2), respectively, duplicated the effects of the proteases on keratinocytes, which expressed mRNA for both receptors. Trypsin increased tyrosine phosphorylated proteins and intracellular free calcium concentrations. Tyrphostin, pertussis toxin, or H-7 suppressed trypsin- and thrombin-induced GM-CSF gene expression. Our results demonstrate that the serine proteases activate thrombin receptors and PAR-2 on keratinocytes, triggering intracellular signaling and then inducing the synthesis of GM-CSF. We speculate that serine proteases modulate the course of physiological and pathological processes in the skin by stimulating keratinocytes to produce the cytokines.
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PMID:Thrombin and trypsin induce granulocyte-macrophage colony-stimulating factor and interleukin-6 gene expression in cultured normal human keratinocytes. 906 88

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