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

Cytokine release and clinical side effects resulting from the use of OKT3 and BMA 031 monoclonal antibodies in the treatment of kidney graft recipients were evaluated and compared. The rise observed in serum levels of interferon gamma. TNF alpha, and IL-8 was similar after administration of either monoclonal antibody. Furthermore, both OKT3 and BMA 031 resulted in rapid disappearance not only of virtually all T cells, but also of substantial percentages of all major leukocyte populations from the circulation; this effect is probably due to cytokine release activating endothelial cells and thereby causing extravasation even of leukocytes not specifically recognized by the administered antibodies. Evidence has thus been obtained that BMA 031 is as potent as OKT3 in inducing unequivocal signs of T cell activation in vivo. However, while OKT3 therapy was accompanied by adverse side effects in our study as in previous ones, we saw no such reactions in any of the patients receiving BMA 031. This contrast might be due to different mechanisms of leukocyte activation possibly inducing other mediators in the case of OKT3, which then, in combination with the cytokines, could generate treatment-associated morbidity.
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PMID:Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal antibody treatment. 140 Aug 97

Putative tissue receptors for leukocyte attractants, including neutrophil attractant/activation protein-1 (interleukin 8, NAP-1/IL-8), have been implicated in the regulation of neutrophil emigration into the tissues. An in-situ binding assay and an ex-vivo autoradiographic approach were used to investigate the binding of radiolabeled NAP-1/IL-8 to human and animal skin. These methods revealed the presence of saturable NAP-1/IL-8-binding sites on the endothelial cells of venules and veins but not arteries or capillaries of the dermis. In addition, the binding of NAP-1/IL-8 to dermal macrophages and perivascular mast cells was observed. We suggest that the NAP-1/IL-8-binding sites described here could be involved in the regulation of NAP-1/IL-8-induced neutrophil emigration.
Cytokine 1992 Sep
PMID:Binding of neutrophil attractant/activation protein-1 (interleukin 8) to resident dermal cells. 142 Sep 95

Quantitative studies of cytokine gene expression in vivo are necessary in order to properly describe the cytokine network and to elucidate its role in skin inflammation. Ideally, one should be able to follow cytokine gene expression in epidermal, dermal, and blood compartments. However, such studies are limited by small amounts of available material. Here we report a polymerase chain reaction (PCR) cDNA amplification protocol useful for quantification of specific mRNAs in small skin samples. We found that analysis of dilution series of each sample permitted establishment of quantitative PCR amplification conditions using only picogram to nanogram amounts of total RNA. Cytokine mRNA amounts could then be measured relative to an internal standard species, co-reverse transcribed, and co-amplified with the cytokine species as a measure of cDNA input. Large numbers of samples can be screened rapidly with initial short dilution series identifying cytokine-positive samples and the correct dilution range for each, followed by closer analysis in this range. Epidermal samples obtained through curettage of a small skin area, 2-mm dermal biopsies from the scraped sites, and a few blood drops from the biopsy sites all yielded sufficient RNA for analysis by this protocol. Any mRNA of known sequence can be studied. We analyzed interleukin 8 mRNA levels in more than a hundred epidermal samples from patients and normal test persons and found a variation over several orders of magnitude that seemed to follow the degree of inflammation of the skin.
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PMID:Use of the polymerase chain reaction in quantification of interleukin 8 mRNA in minute epidermal samples. 146 97

Gro beta and IL-8 are two members of the small induced secreted (SIS) cytokine family (C-X-C subgroup) with proinflammatory activities on neutrophils. In order to assess whether or not the interaction with their receptors results in similar biological actions, we compared the two cytokines in five different bioassays. Gro beta showed similar biological activities as IL-8 in tests of chemotaxis, induction of the respiratory burst, and induction of interleukin 6 (IL-6) production. However, for two other biological activities: augmentation of the expression of CD11b on the cell surface and rapid elevation of the intracellular calcium concentration, maximal effects required 100 times more gro beta than IL-8. Taken together, these results suggest that the stimulation of the IL-8 or gro beta receptor evokes three similar responses, but that only the activation of the IL-8 receptor and not that of gro beta results in elevated CD11b expression and calcium mobilization in human neutrophils.
Eur Cytokine Netw
PMID:The biological activities of gro beta and IL-8 on human neutrophils are overlapping but not identical. 147 97

It is evident from this review that TNF exhibits complex interactions with other cytokines at the level of production and in its effects. Studies designed to determine the role of TNF in the animal models or cell culture system using pure recombinant molecules have revealed that TNF never operates by itself, but instead operates within a network of cytokines. First, the multitude of exogenous as well as endogenous signals, which induce TNF production, concomitantly also stimulate the production of a battery of other inflammatory cytokines: IL-1, IL-6, IL-8, multiple CSFs, IFN, and TGF-beta. Moreover, TNF itself stimulates the production of most of these cytokines. Thus even when pure recombinant TNF is used, it readily generates the production of other interactive cytokines. This apparent redundancy in the production of cytokines with overlapping effects presumably has protective advantage for the host. Furthermore, interaction of these cytokines is more economical and amplifies the responses to subtoxic doses of potentially harmful cytokines. Cytokine interaction may lead to either synergistic (as for many TNF-IL-1 interactions) or antagonistic effects (TNF and TGF-beta, for example). These may depend on (1) the modulation of receptor expression of one cytokine by another (IFN-gamma-enhancing receptor expression for TNF, and TGF-beta down-regulation of IL-1 receptors), (2) stabilization of the cytokine message by one another (induction of IL-6 by TNF or IL-1), (3) interactions at the level of signal transduction, (4) gene expression, or (5) at the posttranslational level. Thus the receptor repertoire, which is a function of the cell type and stage of development, actually determines the net effects of a particular combination of interactive cytokines. Clearly, the mechanisms of these interactions will need to be elucidated to better understand their biological function and to permit cytokines to be used clinically to the advantage of the host.
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PMID:Relationship of TNF to interleukins. 155 Aug 74

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
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PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

Cytokine-stimulated human osteosarcoma cells (MG-63) secrete several related chemotactic factors, including the neutrophil-activating protein interleukin 8 (IL-8) and the monocyte chemotactic protein (MCP)-1. We describe the isolation and characterization of two novel monocyte chemotactic factors from this tumor cell line. Although these proteins copurified with MCP-1 and IL-8 on heparin-Sepharose, they could be separated by cation-exchange fast protein liquid chromatography and reverse-phase high-performance liquid chromatography. The corresponding 7.5- and 11-kD proteins were NH2-terminally blocked but were identified by sequencing peptide fragments. They showed a primary structure mostly related to that of MCP-1 and were therefore designated MCP-2 and MCP-3, respectively. These molecules can be classified in a subfamily of proinflammatory proteins characterized by the conservation of cysteine residues. MCP-2 and MCP-3 are also functionally related to MCP-1 because they specifically attract monocytes, but not neutrophils, in vitro. The chemotactic potency (specific activity) was comparable for all three MCPs. Intradermal injection of these proteins in rabbits resulted in selective monocyte recruitment in vivo. Since tumor cells are good producers of leukocyte chemotactic factors, it could be questioned whether these molecules can indirectly control tumor growth by attracting leukocytes or whether they rather promote invasion by the secretion of proteases from the attracted cells.
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PMID:Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. 161 66

A coherent view of the role of cytokines in inflammatory eye disease is emerging as a result of studies both in man and experimental animals. Cytokines have been demonstrated in ocular tissue obtained from patients with intraocular inflammation (uveitis) (gamma interferon, IL-2) and have been shown to induce inflammation in experimental animals after intraocular injection [(IL-1, IL-6, IL-8, tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF)]. Several unique features of the immunology of the eye such as the immunosuppression associated with anterior chamber associated immune deviation (ACAID) may be due to the effects of cytokines. Similarly, common complications of ocular inflammation such as glaucoma, keratic precipitates, retinal (macular) oedema and neovascularization may be mediated by cytokines. Understanding of the role of cytokines in inflammatory eye disease has the potential to lead to the development of therapies to abrogate the effects of these important mediators of the inflammatory response.
Cytokine 1992 Jan
PMID:The role of cytokines in the pathogenesis of inflammatory eye disease. 161 54

The murine macrophage inflammatory proteins-1 alpha (MIP-1 alpha) and MIP-1 beta are distinct but closely related cytokines. Partially purified mixtures of the two proteins affect neutrophil function and cause local inflammation and fever. The particular properties of MIP-1 alpha have not been well studied, although it has been identified as being identical to an inhibitor of haemopoietic stem cell growth. We have expressed MIP-1 alpha in yeast cells and purified it to sequence homogeneity. Structural analysis of this biologically active material by circular dichroism and fluorescence spectroscopy confirms that MIP-1 alpha has a very similar secondary and tertiary structure to platelet factor 4 and interleukin 8 with which it shares limited sequence homology. The in-vitro stem cell inhibitory properties have been confirmed using a range of murine progenitor cells including purified bone marrow progenitor cells (FACS-1), the FDCP-mix A4 cell line, and spleen colony forming unit (CFU-S) populations. Plateau levels of inhibition of stem cell growth were achieved using concentrations of 0.15 micrograms/ml MIP-1 alpha. We have also demonstrated that MIP-1 alpha is active in vivo: 5 micrograms of MIP-1 alpha per mouse given as a bolus injection, protects stem cells from subsequent in-vitro killing by tritiated thymidine. MIP-1 alpha was also shown to enhance the proliferation of more committed progenitor granulocyte macrophage-colony forming cells (GM-CFC) in response to granulocyte macrophage-colony stimulating factor (GM-CSF).
Cytokine 1992 Jan
PMID:Biological and structural properties of MIP-1 alpha expressed in yeast. 161 59

Interleukin-8 (IL-8/NAP-1), the neutrophil-activating peptide 2 (NAP-2), and formyl-peptides (fMLP) have been described as potent stimulators for human neutrophils (PMN). We have compared the mechanism of signal transduction induced by these factors during neutrophil activation (elastase release), by using activators and inhibitors and by direct measurement of the enzymatic activity of kinases. Moreover, costimulation kinetics of the combined factors were analyzed. Our results show that each of these stimulators induces elevated levels of cAMP, indicating the activation of adenylate-cyclase. Further results obtained with the kinase inhibitor H-7 and the cAMP analogue dibutyryl-cAMP (dbcAMP) gave evidence that cAMP-dependent kinases are involved in the down-regulation of the activation process. Degranulation could not be prevented by the inhibitor W-7, nor did the treatment of cells with calcium ionophore (A23187) lead to elevation of intracellular calcium levels. Both phenomena exclude the participation of calcium calmodulin-dependent kinases. Further results obtained with the novel protein kinase C (PKC) inhibitor BM 41440 as well as by direct measurement of PKC enzyme activity demonstrated the involvement of PKC in fMLP-mediated stimulation but not with IL-8/NAP-1 or NAP-2. Analysis of costimulation experiments conducted with these three factors and TPA confirmed these results and gave evidence that fMLP activates two different signaling pathways, one of which is PKC dependent, while the other is not. Moreover, our data indicate that NAP-2, IL-8/NAP-1, and fMLP use identical PKC-independent transduction mechanisms.
Lymphokine Cytokine Res 1991 Apr
PMID:Neutrophil-activating polypeptides IL-8 and NAP-2 induce identical signal transduction pathways in the regulation of lysosomal enzyme release. 165 69


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