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

Prognosis in myelodysplastic syndrome (MDS) is not only correlated closely with blast cell count in bone marrow and chromosomal abnormalities but also correlated with decreased leucocyte count and function leading to acquisition of lethal infections. Recently, clinical trials in MDS have focused on the application of haemopoietic growth factors such as G-CSF or GM-CSF, which have proven to increase neutrophil count and function. However, these cytokines carry the risk of stimulating the malignant clone, particularly in patients with increased blast cell count. Therefore, investigation of cytokines which are able to stimulate neutrophil function without the potential risk of stimulating haemopoietic progenitor cells may be relevant for MDS. As the stimulatory effect of interleukin-8 on neutrophil function is well known, we investigated whether recombinant human IL-8 is also able to improve the function of neutrophils gained from patients with MDS. Using three different techniques--the E. coli killing assay (8 patients), the production of reactive oxygen as determined by cytochrome c reduction (7 patients) and chemiluminescence (8 patients)--a significant stimulation of neutrophil function at a concentration of 10 nm IL-8 was found in all test systems. No correlation with FAB classification was evident. On the other hand, IL-8 only mildly stimulated growth of myeloid progenitor cells in bone marrow culture of healthy individuals and MDS patients. This minimal stimulation was blocked by a neutralizing antibody directed against GM-CSF, suggesting an indirect effect of IL-8 via secondary GM-CSF release. Thus, IL-8 is able in vitro to repair the functional abnormalities of neutrophils from patients with MDS but has only a marginal influence on myeloid progenitor cells.
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PMID:Recombinant human interleukin-8 restores function in neutrophils from patients with myelodysplastic syndromes without stimulating myeloid progenitor cells. 838 40

The activity of four recombinant human cytokines on porcine neutrophils was evaluated. Porcine neutrophils were treated with varying doses of recombinant human tumour necrosis factor-alpha (rHu-TNF), interferon-gamma (rHu-IFN), interleukin-8 (rHu-lL-8), or granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF). The function of treated neutrophils was compared with that of non-treated controls in the following assays: antibody-independent neutrophil cytotoxicity (AINC), antibody-dependent cell-mediated cytotoxicity (ADCC), iodination, Staphylococcus aureus ingestion, cytochrome C reduction, random migration, and chemotaxis. Treatment with rHu-TNF produced significant (P < 0.05) depression of neutrophil random migration (2.5, 25, and 250 ng ml-1 rHu-TNF) and iodination (250 ng ml-1) and a near significant (P = 0.08) depression in ADCC (250 ng ml-1). Treatment with 25,000 U ml-1 of rHu-IFN caused a significant increase in AINC. At lower doses of rHu-IFN, there was a trend (0.05 < P < or = 0.08) toward depression of AINC (250 U ml-1) and ADCC (25 U ml-1) and enhancement of iodination (250 U ml-1). Treatment with 50 ng ml-1 of rHu-IL-8 caused a near significant increase (P = 0.06) in AINC. There were no significant differences noted when porcine neutrophils were treated with rHu-GM-CSF (2.5-2500 U ml-1). No synergism was noted between rHu-TNF and rHu-IFN.
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PMID:Effect of recombinant human cytokines on porcine neutrophil function. 839 2

Endothelial cells are critical elements in the evolution of all types of cutaneous inflammation. They participate through the synthesis and secretion of pro-inflammatory cytokines, including interleukin 1 (IL-1), IL-6, and IL-8, as well as M-CSF, G-CSF, GM-CSF, gro alpha, and MCP. They also express a series of cell-surface proteins and glycoproteins known as cell adhesion molecules that allow circulating leukocytes to bind to endothelial cells and allow endothelial cells to bind to matrix proteins. The regulated expression of these molecules, including those in the integrin, immunoglobulin gene, and selection families, allows for the precise trafficking of circulating leukocytes to sites of inflammation, injury, or immunologic stimulation in the skin. Furthermore, emerging evidence clearly indicates that selected differences exist between endothelial cells of the microvasculature and those that line large blood vessels. These include differences in secreted products, differences in the expression of cell adhesion molecules, and differences in cytokine-induced regulation of commonly expressed cell adhesion molecules, among others. Thus, a precise delineation of the biology of cutaneous microvascular endothelial cells is important to our understanding of cutaneous inflammation.
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PMID:Role of microvascular endothelial cells in inflammation. 842 79

After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)-1, now re-named IL-1 receptor antagonist (IL-1ra). In this study we have examined the production of IL-1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL-1ra transcripts, which were considerably augmented after treatment with lipopolysaccharides (LPS) and cytokines [IL-4, granulocyte (G)- and granulocyte macrophage (GM)-Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL-1 ra transcripts were comparable to those observed in endotoxin-stimulated human monocytes. By contrast IL-1 beta, interferon (IFN)-gamma and chemotactic factors (fMLP, C5a and IL-8) failed to promote IL-1ra expression in PMN. IL-1ra induction by LPS reached peak levels at 10 ng/ml after 3-6 h and remained sustained 24 h after stimulation. Induction by LPS and GM-CSF appears to be at the transcriptional level, as assessed by inhibiting mRNA synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL-1ra mRNA. In addition to expressing mRNA, PMN also produce IL-1ra protein. Secretion of IL-1ra was induced in PMN treated with LPS, IL-4 and GM-CSF, but not by IL-1 beta, IFN-gamma and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL-1ra, suggesting that PMN, while exerting a series of pro-inflammatory activities, may also modulate the inflammatory potential of IL-1 in tissues.
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PMID:Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells. 843 89

We have previously shown that although DDAVP (1-deamino-8-D-arginine vasopressin), a synthetic analogue of the natural hormone arginine vasopressin, does not directly promote release of vWf from human umbilical vein endothelial cells (ECs), enhanced release does occur when ECs were exposed to either monocytes or to supernatants recovered from DDAVP-treated monocytes. In the present study, we have found that exposure of monocytes to DDAVP did not increase secretion of interleukins (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha), growth factors G-CSF (granulocyte-), GM-CSF (granulocyte, monocyte-colony stimulating factor), prostaglandins (PG) E2, PGF2 alpha, or PGI2 or purine nucleotides such as ATP and ADP. However, increased levels of platelet-activating factor (PAF) were secreted by DDAVP-treated monocytes in a time- and dose-dependent manner that positively correlated with the enhancement in vWf release from ECs. Moreover, this effect could also be elicited when lipid extracts of these supernatants or purified PAF were added directly to ECs. This response could be inhibited with (+/-)-trans-2,5-Bis(3,4,5-trimethoxyphenyl)-1,3-dioxolane, a specific PAF receptor antagonist, when the ECs were exposed to supernatants from DDAVP-treated monocytes or to pure PAF. The present data indicate that enhanced secretion of PAF from monocytes is one mechanism whereby DDAVP can provoke release of vWf from ECs.
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PMID:Platelet-activating factor secreted by DDAVP-treated monocytes mediates von Willebrand factor release from endothelial cells. 843 98

Hyperplasia of mesangial cells (MCs) precedes or accompanies progressive glomerular scarring, as is seen in chronic glomerulonephritis and diabetic glomerulosclerosis. The mechanisms causing in vivo MC proliferation and production of extracellular matrix (ECM) are incompletely understood. Cell culture studies have demonstrated that MCs produce as well as react to various polypeptide cytokines. Thus, MCs have the potential to generate soluble mediators which can, in a paracrine fashion, attract and activate inflammatory cells (platelets, monocyte-macrophages, granulocytes), for example by IL-6, IL-8, MCP-1 and GM-CSF, and exert autocrine effects on MCs themselves, such as by promoting MC proliferation (by PDGF, IL-1, IL-6) or ECM production (by TGF-beta, IL-1). Recent in vitro results have revealed that specific non-soluble ECM components (collagen III, IV; laminin) also affect MC behavior with regard to adhesion, cell replication, ECM production as well as their response to cytokines. The latter effect appears to be mediated by alterations of cytokine receptor expression on MCs in the presence of the ECM components. "Cross-talk" between MCs, cytokines, ECM and inflammatory cells is likely to be of great importance in the regulation of the MC phenotype and may play a prominent role in the initiation and progression of glomerular inflammation. First in vivo findings in rats with experimental glomerular disease and in kidney biopsies from patients with glomerulonephritis have supported this concept by demonstrating abnormal MC expression of cytokines, their receptors and ECM proteins. These MC products may promote the recruitment and activation of inflammatory cells and perpetuate MC proliferation as well as ECM build-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines and mesangial cells. 846 21

Mast cells and basophils are multifunctional effector cells of the immune system. Both are myeloid cells and originate from multipotent hemopoietic progenitor cells. Usually, human basophils complete their differentiation in the bone marrow. In contrast, mast cells usually undergo differentiation in extramedullary organs. During the past few years, growth factors for human basophils and a growth factor for human mast cells have been identified. Interleukin-3 is the most potent differentiation factor for human basophils and activates mature basophils via high affinity binding sites. Other basophil agonists are GM-CSF, IL-5, NGF and certain chemokines (IL-8, MCP-1). Mast cells apparently loose cytokine binding sites during mastopoiesis and as mature cells, do not express detectable amounts of IL-3R, GM-CSFR or IL-8R. However, in contrast to other myeloid cells, mast cells express SCF receptor/c-kit during mastopoiesis and on mature cells. Furthermore, the ligand of c-kit, SCF, induces differentiation of human mast cells from their progenitor cells and upregulates effector functions in mature mast cells.
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PMID:Cytokines involved in growth and differentiation of human basophils and mast cells. 852 98

We present a detailed analysis of cytokine expression patterns of the two permanent human bone marrow stromal cell lines, L87/4 and L88/5. These cell lines, previously established in our laboratory, are highly radiotolerant without cell detachment and support long-term cultures of CD(34+)-enriched human cord blood cells. RT-PCR analysis of 22 different cytokines or cytokine receptor mRNAs showed an almost identical expression pattern in the two stromal cell lines compared to primary human Dexter-type stroma. Since stromal feeder lines employed in long-term cultures usually are irradiated and grown in media containing corticosteroids, we analyzed the impact of irradiation and dexamethasone on cytokine production in the two cell lines by RT-PCR, Northern blot analysis, bioassays, and RIAs. By RT-PCR analysis, constitutive mRNA expression of c-kit, G-CSF, GM-CSF, IL-1 beta, IL-6, IL-7, IL-8, IL-11, Kit ligand (KL), LIF, M-CSF, MIP-1 alpha, TGF-beta, and TNF-alpha was demonstrated in both cell lines, with L87/4 a more potent cytokine producer than L88/5. Northern blot data showed an increase in mRNA levels for GM-CSF, IL-1 beta, and LIF by irradiation and IL-1 alpha treatment in both cell lines. IL-1 alpha-induced GM-CSF, IL-1 beta, IL-6, IL-11, and LIF mRNA levels were reduced by the addition of dexamethasone, whereas dexamethasone had no influence on the amounts of IL-1 alpha-induced G-CSF mRNA. L87/4 and, to a lower extent, L88/5 cells showed dexamethasone-dependent increases in KL mRNA, while KL mRNA levels were not stimulated by IL-1 alpha.
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PMID:Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines. 853 85

The scientific interest in the physical interaction of Plasmodium falciparum-infected erythrocytes with host cells stems from the suggestion that excessive binding in the microvasculature leads to severe malaria. The authors studied, therefore, two parasites for their ability to adhere to normal human cells and to induce cytokine production, one parasite lacking a binding capacity (DD2) and one which adhered to CD36+ transfected CHO cells (MCAMP). The MCAMP parasites readily bound to platelets and erythrocytes and to monocytes, polymorphonuclear granulocytes and EBV-transformed B cells as seen by light and electron microscopy. Platelets were frequently attached in large numbers to the infected erythrocyte surface and groups of infected erythrocytes were sometimes held together by several platelets. Nine out of 17 cytokines tested were found to be secreted into the culture supernatants after 35 h of co-cultures containing monocytes or unfractionated peripheral blood mononuclear cells (PBMC) and parasites (IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, IL-1-beta, and GM-CSF). Three additional cytokines were also present in low levels (< 200 pg/ml, IL-2, IL-4, IFN gamma) in the culture supernatants after incubation of the cells for 4 days. TNF alpha, IL-RA, and IL-8 were secreted from polymorphonuclear granulocytes, LGLs and T cells. Platelets and, to a lesser degree, monocytes and T cells secreted large amounts of TGF beta (10-30 ng/ml). Cytokines may participate in the pathogenesis but also the suppression of immune responses seen during acute malarial infections.
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PMID:Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and secretion of cytokines (IL-1-beta, IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, GM-CSF. 855 86

Numerous cytokines are present within inflammatory foci. Interleukin-1 (IL-1) and tumour necrosis factor (TNF) play a major role in coordinating mechanisms which command inflammation. Upon their action, many different cells produce lipidic mediators, proteolytic enzymes, and free radicals, all directly responsible for the noxious effects observed. IL-1 and TNF exert cytotoxic effects on vascular endothelium, cartilage, bone and muscle. Such cytokines as interferon-gamma, IL-3 or granulocyte-macrophage colony stimulating factor amplify the inflammatory response by increasing the production of IL-1 and TNF. The latest trigger the release of chemokines such as IL-8 and macrophage chemoattractant protein-1, the chemotactic activity of which participates in the recruitment of leukocytes within the foci of inflammation. IL-6, abounds in inflammatory processes and induces the production by hepatocytes of acute phase proteins. The same applies to IL-1, TNF, IL-11, the leucocyte inhibitory factor, and the transforming growth factor-beta. The later also processes a number of anti-inflammatory activities and, like IL-4, IL-10 and IL-13, can inhibit IL-1 and TNF production. Such property has also been mentioned for interferon-alpha. These anti-inflammatory cytokines can also counteract some of the IL-1 and TNF activities such as those reported during the coagulation process. Furthermore, these anti-inflammatory cytokines can induce the production of the IL-1 receptor antagonist which prevents the activities initiated by IL-1. Soluble TNF receptors, released during inflammation, are the direct inhibitors for TNF. Glucocorticoids, produced following a cascade of events initiated by IL-1, TNF and IL-6, involving the neuroendocrine axis, also inhibit proinflammatory cytokine productions. The concept of "cytokine network" therefore, perfectly illustrates the participation of these mediators in inflammation mechanisms.
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PMID:[Cytokines in inflammation]. 856 67


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