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)

Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1 alpha and TNF-alpha induce 51Cr-labelled PMNL migration across monolayers of umbilical vein endothelium via an endothelial cell-dependent mechanism. Here we investigated the interaction of PMNL with fibroblasts, since PMNL probably encounter such cells in many tissues once they traverse the vascular wall. TNF-alpha, but not IL-1 alpha, was found to activate fibroblast monolayers, grown on polycarbonate filters, to stimulate PMNL transfibroblast migration. This was a time- and fibroblast-dependent process which required fibroblast protein synthesis, as indicated by inhibition with cycloheximide. The effect of TNF-alpha was not related to fibroblast chemotactic factor production (primarily IL-8), or to ICAM-1 up-regulation, since IL-1 was as active as TNF-alpha in this respect, without activating fibroblasts to support PMNL transfibroblast migration. Antiserum to IL-8, present during the assay, did not inhibit PMNL migration across the monolayers. The PMNL migration was highly dependent on the function of both CD11a (LFA-1) and CD11b (MAC-1) PMNL adhesion molecules, since monoclonal antibodies to either inhibited migration by about 80%. The results suggest a distinct activation by TNF-alpha of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-alpha in inducing extravascular accumulation of PMNL during inflammation.
Immunology 1991 Sep
PMID:Tumour necrosis factor-alpha but not interleukin-1 induces polymorphonuclear leucocyte migration through fibroblast layers by a fibroblast-dependent mechanism. 193 64

In order to elucidate the role of inflammatory cytokines in the central nervous system (CNS), we examined whether IL and TNF-alpha induce cells in the CNS to produce two newly identified leucocyte chemo-attractants, IL-8 and monocyte chemotactic and activating factor (MCAF). Several human astrocytoma and glioblastoma cell lines expressed high levels of IL-8 and MCAF mRNA in vitro upon stimulation with IL-1 and TNF-alpha. In particular, an astrocytoma cell line U373MG subclone responded markedly to IL-1 with high expression levels of IL-8 and MCAF mRNA as well as IL-6 mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 and appeared as early as 30 min to 1 hr after IL-1 stimulation, confirming that these are early inducible genes. The production of IL-8 and MCAF in the U373MG cell culture supernatants was confirmed by a competitive radioimmunoassay (RIA) as well as chemotactic activities on human neutrophils and monocytes. IL-1-induced IL-8 and MCAF mRNA expression appeared to occur at least at the transcriptional level as revealed by a nuclear run-off assay. Moreover, IL-1 treatment increased the half-life of IL-8 and MCAF mRNA markedly, suggesting that increased mRNA stability was also responsible for the enhanced gene transcription. These data suggest that IL-1 and TNF-alpha induce astrocytes to produce IL-8 and MCAF transcriptionally and post-transcriptionally, both of which may be responsible for leucocytosis seen in inflammation of the CNS.
Immunology 1991 Sep
PMID:IL-1 and TNF-alpha induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line. 193 74

Human epidermal keratinocytes constitutively produce a variety of cytokines, including neutrophil chemotactic peptide named epidermal cell-derived thymocyte-activating factor, which has been later confirmed to be interleukin 1 (IL-1). Because recombinant IL-1 lacks chemotactic activity, in the present study, we examined the exact nature of the neutrophil chemotactic peptide in the culture supernatant of normal human epidermal keratinocytes. Normal human epidermal keratinocytes produced a neutrophil chemotactic factor, which was also chemotactic for T lymphocytes. Molecular sieve chromatography revealed an approximate molecular size of 11,000 daltons. The activity was retained after heating at 100 degrees C for 10 min, and at a pH between 4 and 11, but was partially inactivated at pH 3, or by trypsin treatment. The chemotactic activity was not inhibited by the treatment with anti-IL-1 antibody. Its production by keratinocytes was stimulated by IL-1 and lipopolysaccharide but not by UV irradiation, tumor necrosis factor-alpha or by interferon-gamma. The neutrophil chemotactic activity in vivo was confirmed by the intradermal injection of the factor into guinea pigs. Blocking study with monoclonal antibodies against NAP-1/IL-8 confirmed that the neutrophil chemotactic factor is IL-8.
Tohoku J Exp Med 1990 Sep
PMID:Normal human epidermal keratinocyte-derived neutrophil chemotactic factor. 207 75

Isolation of the human neutrophil activating protein (NAP) interleukin 8 (IL8) from leukocytes has revealed that it is structurally related to beta-thromboglobulin (beta TG) from platelets. Both these proteins occur as natural mixtures of multiple forms, differing from each other by unequal truncation at the NH2 terminus. In this study we have compared IL8 and beta TG forms for in vitro and in vivo neutrophil activation. In contrast to IL8, none of the beta TG forms were found to exert granulocyte chemotactic activity in vitro, as measured in the agarose assay. However, fractions rich in the most extensively processed forms of beta TG (e.g. NAP-2) as well as pure NAP-2 did induce lactoferrin release from granulocytes, whereas fractions containing only the longer forms (e.g. connective tissue-activating peptide III) were inactive. In order to observe this in vitro effect, about 10-fold less IL8 (10 nM) than NAP-2 was required. In the presence of a vasodilator substance low doses (2-20 pmol) of IL8 and the shorter forms of beta TG caused granulocyte accumulation and plasma leakage in rabbit skin whereas the longer forms of beta TG again failed to do so. Finally, granulocytosis induction following i.v. injection was found to occur with NAP-2. At the maximal dose tested (250 pmol), this in vivo effect of NAP-2 was less pronounced than that of IL8. In the case of IL8, NH2-terminal processing did not seem to affect granulocyte stimulatory activity. It should be noted, however, that the extent of processing of IL8 is less than that occurring with beta TG. It can be concluded that the platelet factor beta TG, structurally related to the monokine IL8, can also play a role in neutrophil activation during inflammatory reactions.
Eur J Immunol 1990 Sep
PMID:The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. 214 75

Peripheral blood monocytes are important mediators of inflammation via the generation of various bioactive substances, including the recently isolated and cloned chemotactic peptide IL-8. Through cytokine networking, monocyte-derived cytokines are capable of inducing IL-8 expression from non-immune cells. IL-4, a B and T lymphocyte stimulatory factor, has recently been shown to inhibit monocyte/macrophage function, including the ability to suppress monocyte-generated cytokines. We describe the in vitro inhibition of IL-8 gene expression and synthesis from LPS, TNF, and IL-1 stimulated peripheral blood monocytes by IL-4. IL-4 suppressed IL-8 production from stimulated monocytes in a dose-dependent fashion, with partial suppression observed at IL-4 concentrations as low as 10 pg/ml. The IL-4-induced suppressive effects were observed even when IL-4 was administered 2 h post-LPS-stimulation. The IL-4-induced inhibition of IL-8 mRNA expression was dependent on protein synthesis, as the suppressive effects of IL-4 were significantly negated by the addition of cycloheximide. Our findings suggest that IL-4 may be an important endogenous regulator of inflammatory cell recruitment, and adds further support to the potential role of IL-4 as a down-regulator of monocyte immune function.
J Immunol 1990 Sep 01
PMID:IL-4 inhibits the expression of IL-8 from stimulated human monocytes. 220 Aug 23

A cDNA clone of murine macrophage inflammatory protein 2 (MIP-2) has been isolated from a library prepared from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the nucleotide sequence determined. This cDNA was used to clone cDNAs for human homologues of MIP-2 from a library prepared from phorbol myristate acetate-treated and LPS-stimulated U937 cells. Two homologues were isolated and sequenced. Human MIP-2 alpha and MIP-2 beta are highly homologous to each other and to a previously isolated gene, human gro/melanoma growth-stimulating activity (MGSA). These three human genes, MIP-2 alpha, MIP-2 beta, and gro/MGSA, constitute a sub-family within the cytokine family represented by platelet factor 4 and interleukin 8.
J Exp Med 1990 Sep 01
PMID:Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. 220 51

The role(s) of novel chemotactic cytokines as mediators in the pathogenesis of many acute and chronic disease states is becoming increasingly apparent. One of these cytokines, interleukin 8, is a product of both immune and non-immune cells. In this manuscript, we describe the suppression of IL-8 gene expression from stimulated monocytes by IL-4, while IL-4 had no suppressive effects on IL-8 gene expression from stimulated fibroblasts and endothelial cells. Our data suggest that IL-4 may function as an endogenous regulator of monocyte cytokine expression, including the chemotactic cytokine IL-8.
Biochem Biophys Res Commun 1990 Sep 14
PMID:Disparate regulation of interleukin 8 gene expression from blood monocytes, endothelial cells, and fibroblasts by interleukin 4. 220 28

The presence of neutrophils in the synovial joint of patients with rheumatoid arthritis (RA) is thought to be due to the activity of chemotactic factors released by activated cells in the joint. We have shown in this report, for the first time, the abundance of one such factor, interleukin 8 (IL 8), in the synovial fluid of patients both with RA and other non-RA joint diseases, and the spontaneous production of IL 8 mRNA by RA synovial cells in culture. There was no correlation between the levels of chemotactic activity and IL 8 protein, suggesting that other factors with similar neutrophil chemotactic activity are also present in the synovial fluid exudate. In support of this concept neither the level of chemotactic activity nor IL 8 protein levels correlated with neutrophil or leukocyte infiltration, indicating that the mechanism of migration into the inflammatory environment of the joint is complex. Such migration is likely to be due to a number of chemotactic signals in addition to IL 8, which may either synergize with, or inhibit, the action of IL 8.
Eur J Immunol 1990 Sep
PMID:Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. 220 7

LPS and mitogen-stimulated mononuclear cells secrete a cytokine, which is able to activate the PMNL-arachidonate-5-lipoxygenase. This cytokine has been proven to be identical with the recently characterized novel neutrophil-activating peptide NAP/IL-8. NAP/IL-8 is able to activate human PMNL for release of LTB4, omega-oxidized LTB4, and 5-HETE in the presence of exogenous AA. Half-maximal concentration of NAP/IL-8 for release of LTB4 has been found to be near 4 x 10(-8) mol/liter. Time course studies revealed rapid activation of PMNL, with maximal release of LTB4 within the first 10 min with a decline up to 40 min. High amounts of omega-oxidized LTB4 were detected up to that time. Significant amounts of AA-5-LO-products can be detected only when PMNL were stimulated with NAP/IL-8 in the presence of exogenous AA. The concentration of AA necessary for half-maximal LTB4 release has been found to be 3 x 10(-6) mol/liter. In the presence of 8 x 10(-9) mol/liter [3H]AA, NAP/IL-8 (10(-9) to 10(-7) mol/liter) did not induce the production of LTB4, omega-oxidized LTB4, or 5-HETE. In addition, PMNL prelabeled with [3H]AA did not release either [3H]AA or 5-lipoxygenase metabolites when stimulated with NAP/IL-8 (10(-9) to 10(-7) mol/liter), indicating that NAP/IL-8 apparently does not activate cellular phospholipases/diacylglycerol-lipases. Apart from FMLP, C5a, and PAF NAP/IL-8 is the fourth clearly characterized neutrophil chemotaxin able to activate the PMNL-5-lipoxygenase. The detection of large amounts of NAP/IL-8, arachidonic acid, as well as LTB4-like material, in lesional material of patients with psoriasis points towards a possibly important role of NAP/IL-8 in amplifying inflammatory processes by induction of LTB4-production.
J Exp Med 1989 Sep 01
PMID:The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate. 254 66

LPS-stimulated human mononuclear cells have recently been shown to produce large amounts of a novel neutrophil-activating cytokine termed neutrophil-activating peptide NAP/IL-8. This chemotactic factor has in the meantime been biochemically and functionally well characterized. We now report on four distinct murine mAb directed against this peptide. All four mAb are different in respect to isotype and IEF pattern. The cross-reactivity with partially homologous peptides like beta-thromboglobulin and platelet factor 4 showed defined differences. With the use of these antibodies we were able to detect solid phase as well as soluble NAP/IL-8 as tested in a sandwich-ELISA. Also dose-dependent neutralization of NAP/IL-8 chemotactic activity in the Boyden chamber chemotaxis assay was observed. Immunoaffinity columns prepared with these four mAb bound NAP/IL-8 from supernatants of LPS-stimulated mononuclear cells. Furthermore, Western immunoblots showed a single protein band in the expected region of Mr of 10 kDa with all four mAb presented.
J Immunol 1989 Sep 01
PMID:Production and characterization of monoclonal antibodies against the novel neutrophil activating peptide NAP/IL-8. 266 11


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