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)

Two cDNAs coding for distinct interleukin 8 (IL-8) receptors, IL-8R1 [Murphy and Tiffany (1991) Science 253, 1280-1283] and IL-8R2 [Holmes, Lee, Kuang, Rice and Wood (1991) Science 253, 1278-1280] have been reported, and biochemical studies on human neutrophils have revealed two proteins (p70 and p44) that bind IL-8 with high affinity [Moser, Schumacher, von Tscharner, Clark-Lewis and Baggiolini (1991), J. Biol. Chem. 266, 10666-10671]. We have cloned the cDNA coding for IL-8R1 from a library of differentiated HL-60 cells. Transfection of this cDNA into Jurkat cells resulted in the expression of high-affinity binding for IL-8 and two related cytokines, GRO alpha and neutrophil-activating peptide 2 (Kd 0.5-1.0 nM). Northern-blot analysis with the IL-8R1 cDNA as probe revealed abundant expression of transcripts of different size in human neutrophils and low-level expression of a single RNA species in HL-60 cells differentiated with dimethyl sulphoxide and retinoic acid. Because of the extensive nucleotide sequence similarity of the cDNAs for IL-8R1 and IL-8R2, the reverse-transcription PCR method was used for analysis of RNA expression in myeloid and lymphoid cells, 19 cell lines established from human primary melanomas or metastases, two melanocyte and one fibroblast cell lines. IL-8R1 mRNA transcripts were expressed at high levels in neutrophils, and to a lesser extent in blood monocytes and the myeloid cell lines, HL-60 and AML 193, but were not found in THP-1 cells, lymphocytes and Jurkat cells. IL-8R2 mRNA transcripts, by contrast, were found in all blood cells and related cell lines, as well as in all melanoma, melanocyte and fibroblast cell lines tested. As for IL-8R1, IL-8R2 mRNA expression was highest in neutrophils. These results suggest that IL-8R1 and IL-8R2 may both be involved in neutrophil activation by IL-8 and related cytokines, and presumably correspond to p70 and p44, the receptors that were identified biochemically. Possible IL-8 functions on lymphocytes and melanoma cells, e.g. chemotaxis and proliferation, must be independent of IL-8R1 and may be mediated by IL-8R2.
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PMID:Expression of transcripts for two interleukin 8 receptors in human phagocytes, lymphocytes and melanoma cells. 836 81

Treatment of normal primary human keratinocytes with phorbol 12-myristate 13-acetate (PMA) or phorbol 12-13 dibutyrate (PDBu) (100 ng/ml, 6-40 h) followed by two-dimensional (2-D) gel electrophoresis (isoelectric focusing) and microsequencing identified three polypeptides (phorbolin 1, M(r) = 19.9 kDa; phorbolin 2, M(r) = 19.7 kDa; and interleukin-1 (IL-1) receptor antagonist, IL-1ra, M(r) = 19.5 kDa) that are upregulated eight times or more by the phorbol esters and that are highly expressed in noncultured psoriatic keratinocytes. The response was not elicited by other effectors tested including second messengers (Bt2cAMP, Bt2cGMP), cytokines (basic fibroblast growth factor, transforming growth factor-alpha, IGF-II, tumor necrosis factor-alpha, and -beta, interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-6, IL-7, IL-8, interferon-alpha, and -gamma), and other substances (Ca++, dexametasone, retinoic acid, lipopolysaccharides) and it was partially reversed by staurosporine, a strong inhibitor of protein kinase C. The results are taken to imply that the protein kinase C signaling pathway may be altered in psoriatic keratinocytes.
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PMID:Evidence for an altered protein kinase C (PKC) signaling pathway in psoriasis. 840 24

Retinoic acid (RA) is a multifunctional drug that is particularly effective at preventing the development of multiple primary oral squamous cell carcinomas. A portion of this activity is due to the inhibition of tumor angiogenesis. It has been thought that RA influences tumor angiogenesis only via its interactions with the tumor cells themselves. Here, we test the hypothesis that the drug can also block neovascularization by directly inhibiting the angiogenic activity of normal endothelial cells. Clinically achievable doses of RA rapidly caused large- and small-vessel endothelial cells to become refractory to stimulation of migration either by tumor-conditioned media or purified angiogenic factors (a-fibroblast growth factor (aFGF), bFGF, vascular endothelial GF, platelet-derived GF, TGF beta-1, and IL-8). However, RA had little effect on their proliferation. Inhibition of migration was complete within 3 hours and was reversed 36 hours after drug removal. The migration of human oral keratinocytes was not sensitive to RA, whereas the migration of fibroblasts and vascular smooth muscle cells was inhibited. To determine if systemic RA affected neovascularization, rats were given 1 mg/kg/day of all-trans RA and their angiogenic potential was tested by implanting pellets of tumor-conditioned media into their avascular corneas. This treatment rendered the rats unable to mount a neovascular response in their corneas. These data demonstrate that RA directly affects endothelial cells, rapidly and reversibly inhibiting their ability to migrate toward a variety of stimuli in vitro and halting the formation of new vessels in vivo. These direct effects on vascular cells seem likely to contribute to the success of RA as a chemopreventive agent for oral squamous cell carcinoma.
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PMID:Inhibition of squamous cell carcinoma angiogenesis by direct interaction of retinoic acid with endothelial cells. 878 Jan 65

Activin A is a cytokine whose multiple functions have yet to be fully determined. In this study, the role of proinflammatory cytokines in regulatory control of activin A production was shown in synoviocytes and chondrocytes. Additional facets of functional inflammation-related activities of activin A were also determined. Results showed that activin A concentrations in the synovial fluid of patients with rheumatoid arthritis and gout were elevated relative to those in patients with osteoarthritis. Further studies showed that production of activin A by synoviocytes and chondrocytes in culture was stimulated by cytokines such as IL-1, transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma), and IL-8, consistent with previous studies in regard to the control of activin A production in marrow stromal cells and monocytes by cytokines, glucocorticoids and retinoic acid. In addition, the relationship of activin A to IL-6-induced biological activities was investigated. Three major IL-6 activities involved in inflammatory responses were found to be suppressed by activin A. In a dose-dependent manner, activin A efficiently suppressed IL-6-induced proliferation of 7TD1 B lymphoid cells, phagocytic activity of monocytic M1 cells, and fibrinogen production in HepG2. Therefore, it is likely that activin A serves as a suppressor for IL-6, dampening inflammatory responses, and has the potential to perform some previously unrecognized roles in inflammation.
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PMID:Suppression of IL-6 biological activities by activin A and implications for inflammatory arthropathies. 956

Chemokines play a very important role in inflammation and belong to the family of proinflammatory cytokines. They preferentially act on neutrophiles and have no activity on monocytes and eosinophiles. IL-8 is a member of C-X-C chemokines. The IL-8 level is about 150-times higher in the psoriasis affected skin. It suggests that IL-8 may play an important role in the pathogenesis of psoriasis. The precise mechanism of cyclosporine (CsA) and retinoic acid (RA) effects are not known. The aim of the experiment was to find out CsA effect and RA effect on production of IL-8 by THP-1 cell line. THP-1 cell line was cultivated in completed RPMI-1640 medium and stimulated with LPS. The level of IL-8 was evaluated by human ELISA kits. Student's test was used for statistical analysis. It was found out that CsA inhibits IL-8 production by stimulated THP-1 monocyte cell line in dose dependence course. RA promotes IL-8 production by stimulated THP-1 monocyte cell line in dose dependence course. Preincubation experiments with CsA and RA confirmed the previously found effects of these drugs. CsA did not demonstrate cytotoxic effect on THP-1 cell line. (Fig. 7, Tab. 6, Ref. 17.)
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PMID:[Production of IL-8 by the THP-1 monocyte cell line is regulated differently by cyclosporin and retinoic acid]. 958 80

Differentiation therapy with all-trans retinoic acid (ATRA) represents a landmark approach in the treatment of acute promyelocytic leukemia (APL). However, a potentially fatal complication of retinoic acid (RA) syndrome occurs in about a quarter of patients and its pathophysiology is still unclear. In order to investigate whether or not the treatment with ATRA leads to increased elaboration of inflammatory cytokines and adhesion molecules by the APL cells, the expression of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-8, L-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined in the APL cells after induction of differentiation with ATRA in the presence or absence of granulocyte-colony stimulating factor (G-CSF) or IL-3 in the present study. Cytokine elaboration by the treated cells was detected using both Northern blotting and enzyme-linked immunosorbent assay. Our results have shown that ATRA induces an increased expression of IL-8, IL-1beta, TNF-alpha and ICAM-1 in APL cells, which can be amplified by the addition of G-CSF. These data imply that the induction of inflammatory cytokines in APL cells may play an important role in the pathogenesis of RA syndrome. Furthermore, G-CSF, through its potent differentiating activity, may increase the risk of such complications during ATRA treatment.
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PMID:In vitro effect of granulocyte-colony stimulating factor and all-trans retinoic acid on the expression of inflammatory cytokines and adhesion molecules in acute promyelocytic leukemic cells. 1041 49

The main goal of the present study was to investigate the response of the human skin equivalent Apligraf in vitro to the application of irritant substances and its predictivity as a screening tool for cumulative skin irritant potential in humans. Vaseline, calcipotriol, trans-retinoic acid, and sodium lauryl sulfate were applied to Apligraf in vitro for 24 h. Cell viability (lactate dehydrogenase leakage), release and mRNA expression of the proinflammatory cytokines IL-1alpha and IL-8, and morphological changes were assessed. The same products were applied to 30 healthy volunteers in a double-blind, randomized, vehicle-controlled within-subject study. The skin reactions after repeated 24-h applications over 3 weeks under Finn chamber patches were monitored by visual scoring and biophysical methods (trans-epidermal water loss, chromametry, and blood flow). Sodium lauryl sulfate was cytotoxic to Apligraf, and increased the release and expression of cytokines at low (0.2%, 0. 4%), but not at high (0.8%, 1%) concentrations. It induced severe irritancy in vivo. Trans-retinoic acid increased the expression and release of cytokines with no detectable cytotoxicity and showed moderate irritancy in humans. Although calcipotriol did neither affect cell viability nor the production of cytokines, it induced morphological signs of irritation and was mildly irritant for healthy volunteers. Vaseline was innocuous in vivo and induced no changes in Apligraf. In conclusion, the cumulative skin irritation potential of the tested products could be predicted with Apligraf in a sensitive and specific manner, by monitoring cytotoxicity, proinflammatory cytokines, and morphological changes.
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PMID:Use of human skin equivalent Apligraf for in vitro assessment of cumulative skin irritation potential of topical products. 1073 42

A 3- to 8-fold stimulation of interleukin (IL)-8 gene expression by all-trans-retinoic acid (ATRA) was demonstrated in primary cultures of human and monkey tracheobronchial epithelial cells and BEAS-2B serum-sensitive cell line. The effect of ATRA on IL-8 gene expression is dose- and time-dependent. Using cycloheximide, it was observed that new protein synthesis was required for the stimulation. ATRA had no effect on IL-8 messenger RNA stability. A difference in nuclear run-on activity suggests that a transcriptional mechanism is involved in ATRA-enhanced IL-8 gene expression. Promoter-reporter gene transfection studies demonstrated ATRA enhanced IL-8 promoter activity, especially when cells were cotransfected with retinoic acid nuclear receptor-alpha expression vector. Deletion and site-directed mutagenesis analysis revealed the involvement of nuclear factor (NF)-kappaB binding site of the IL-8 gene in ATRA-enhanced promoter activity. Electrophoretic mobility shift assay (EMSA) demonstrated that ATRA enhanced DNA-NF-kappaB complex formation, especially with the p65 subunit. Western blot analysis demonstrated that ATRA did not enhance the protein amount of both the p50 and the p65 subunits in the nuclei. Because ATRA also enhances thioredoxin (TRX) gene expression, the effect of TRX on IL-8 gene expression was examined. IL-8 promoter activity was enhanced in transfected cells by the addition of TRX protein. Treatment of nuclear extracts with TRX also enhanced DNA- NF-kappaB complex formation as observed by EMSA, particularly the p65 subunit. Taking these data together, a novel mechanism is proposed in which ATRA activates promoter activity of IL-8 gene through TRX-dependent NF-kappaB activation.
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PMID:A novel mechanism of retinoic acid-enhanced interleukin-8 gene expression in airway epithelium. 1074 31

Hematopoietic progenitor cell differentiation is associated with the expression of different sets of genes including those encoding membrane bound molecules and cytokines. While expression of the former has meticulously been linked to both lineage specificity and maturation stages and is routinely used in the diagnosis of human leukemias, the production of cytokines has not systematically been analyzed in this respect. Secretion of cyto- and chemokines by HPC has been discussed as a key element of autocrine regulation of cell differentiation and proliferation in normal and malignant hematopoietic cells. Hematopoietic cell lines and their in vitro generated mature progeny were used as a model to investigate the cytokine and chemokine expression pattern prior to and after induction of differentiation. We show that a variety of cytokines are produced by these cells either constitutively or upon stimulation. Low levels of TNF-alpha and IL-8 were widely expressed by immature and mature cells, while peak values of TNF-alpha were detected in promyelocytic NB4 cells, as reported previously. Induction of monocytic differentiation by various agents was associated with upregulation of IL-1 beta and IL-1ra expression, while a differentiation shift to the granulocytic lineage in the presence of retinoic acid (RA) led to a marked increase of macrophage chemoattractant protein-1 (MCP-1) producing cells. These data indicate that lineage determination as well as maturation of hematopoietic cells may not only be associated with expression of specific surface molecules but also with a distinct cytokine expression pattern. Further studies are necessary to show if this holds true for primary leukemic and normal hematopoietic cells.
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PMID:Differentiation associated modulation of the cytokine and chemokine expression pattern in human myeloid cell lines. 1116 29

Investigation of mast cell responsiveness toward retinoic acid (RA) revealed selective promotion of ICAM-3 expression in the human mast cell line HMC-1. This process was dose- and time-dependent and detectable by flow cytometry, Western blot analysis, ELISA, and Northern blot analysis. ICAM-3 modulation was found to be cell-type dependent, detectable also for HL-60 cells and monocytes but not U-937 and only weakly for KU812 cells. Terminally differentiated skin mast cells also failed to up-modulate their ICAM-3, suggesting the requirement for some degree of immaturity for the process. RA-mediated effects on ICAM-1 expression, studied in parallel, were clearly distinct from those on ICAM-3. Investigation of retinoid receptor expression, known to mediate intracellular RA signaling, revealed presence of RAR alpha, RAR gamma, RXR beta, and RXR gamma transcripts in all cell lines studied, and HMC-1 cells were the only line lacking RXR alpha. RAR beta, not expressed at baseline, was induced by RA in a fashion obviously correlating with ICAM-3 up-regulation. Increased ICAM-3 expression was of functional significance, such that processes stimulated or co-stimulated via ICAM-3 (homotypic aggregation, IL-8 secretion) were clearly enhanced upon RA pretreatment, suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense.
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PMID:Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion--evidence for retinoid signaling pathways in the mast cell lineage. 1126 82

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