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)

In order to analyse Th2-type immune responses in sheep by the assay of interleukin (IL)-5 in biological fluids, the ovine IL-5 gene was cloned and expressed in Spodoptera frugiperda Sf9 insect cells using the baculovirus expression vector system. The recombinant product was purified as BAC-OV-IL-5 from the supernatant fluid. The ovine IL-5 was biologically active in a bioassay using IL-5-dependent Baf cells, which have been used previously to specifically detect human IL-5. The specificity of Baf cells for ovine IL-5 was examined by two methods. First, Baf cells only proliferated in response to BAC-OV-IL-5 and did not respond to addition of recombinant ovine cytokines granulocyte-macrophage colony stimulating factor (GM-CSF), IL-1beta, IL-2, IL-3, IL-6, IL-8, stem cell factor (SCF) or IFN-gamma at doses from 0.01 to 1 microg/well. Second, the rat monoclonal antibody to murine IL-5, TRFK-5, neutralized murine, but not ovine, IL-5. However, rabbit antisera to BAC-OV-IL-5 neutralized murine and ovine recombinant IL-5 and abolished responses of Baf cells to IL-5 activity in supernatant fluids from mesenteric lymph node cells (MLNC) of parasitized sheep. The bioassay had a sensitivity to detect 8 ng in a 200 microL assay (40 ng/mL). Thus, the specificity of Baf cells to detect human IL-5 also extends to ovine IL-5 and therefore provides a method for monitoring the production of Th2 immune reactivity in sheep.
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PMID:Characterization of a bioassay for detection of recombinant and native ovine interleukin-5. 1045

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship between endogenous cytokine levels and circulating platelet counts, we measured the serum levels of both thrombopoietic and inflammatory cytokines in the peripheral blood and bone marrow samples from 70 patients with clonal thrombocytosis (CT) caused by myeloproliferative disorders, 28 patients with reactive thrombocytosis (RT), and 35 normal control subjects. The levels of thrombopoietin (TPO), interleukin-6 (IL-6), soluble IL-6 (sIL-6) receptor, IL-11, stem cell factor (SCF), IL-3, and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Platelet counts were significantly higher in both CT and patients with RT (699+/-399x10(9)/L, P<.001; 642+/-200 x 10(9)/L, P<.001; respectively) as compared with the normal control subjects (240+/-47x10(9)/L). The concentrations of cytokines in the bone marrow correlated well with those in the peripheral blood. The endogenous levels of TPO, IL-6, and sIL-6 receptor were significantly higher in both CT and patients with RT than those in normal control subjects. The median level of IL-6 was significantly higher in patients with RT than in patients with CT (40 pg/mL vs. 5 pg/mL; P<.001); however, there was no detectable difference in TPO and sIL-6 receptor levels between the two groups. Significantly higher levels of SCF and IL-8 were also found in patients with CT as compared with those found in normal control subjects (median 2460 pg/mL vs 1995 pg/mL, P<.05; 20 ng/mL vs. 5 ng/mL, P = .001; respectively). Finally, IL-11 and IL-3 levels were undetectable in most patients with thrombocytosis. Our results reveal that the endogenous levels of TPO, IL-6, sIL-6 receptor, IL-8, and SCF are elevated in patients with CT or RT. These cytokines appear to be active mediators involved in the regulation of thrombopoiesis during clonal and reactive thrombocytosis.
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PMID:Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis. 1052 Oct 86

Mast cells are recognized as a new type of immunoregulatory cells capable of producing different cytokines. So far, little is known about the cytokine profile of mature human mast cells isolated from intestinal tissue and cultured in the presence of stem cell factor (SCF). We observed that these cells express the proinflammatory cytokines TNF-alpha, IL-1 beta, IL-6, IL-8, IL-16, and IL-18 without further stimulation. Both IgE-dependent and IgE-independent agonists (e.g., Gram-negative bacteria) enhanced expression of TNF-alpha. Another set of cytokines consisting of IL-3, IL-5, IL-9, and IL-13 was expressed following activation by IgE receptor cross-linking. If mast cells were cultured in the presence of IL-4 and SCF, the production and release of IL-3, IL-5, and IL-13 was increased up to 4-fold compared with mast cells cultured with SCF alone. By contrast, IL-6 expression was completely blocked in response to culture with IL-4. In summary, our data show that mature human mast cells produce proinflammatory cytokines that may be up-regulated following triggering with IgE-independent agonists such as bacteria, whereas activation by IgE receptor cross-linking results in the expression of Th2-type cytokines. IL-4 enhances the expression of Th2-type cytokines but does not affect or even down-regulates proinflammatory cytokines.
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PMID:Human intestinal mast cells are capable of producing different cytokine profiles: role of IgE receptor cross-linking and IL-4. 1060 91

Eosinophils, the major immune effector cells contributing to allergic inflammation and asthma, are profoundly affected by interleukin (IL) 5 with respect to their differentiation, viability, recruitment, and cytotoxic effector functions. IL-5 enhances eosinophil responsiveness to a variety of chemotactic factors via a process called priming, although the molecular mechanism is unknown. In this study, we report that, following IL-5 priming of eosinophils, chemotactic agents including fMet-Leu-Phe, IL-8, and RANTES, promote vigorous transient activation of ERK1 and ERK2. In contrast, these chemotactic factors stimulate weak or indiscernible ERK activation in unprimed eosinophils. Furthermore, this intracellular marker of priming is selective for IL-5-related cytokines, in that it is observed following exposure to IL-5 and granulocyte macrophage-colony stimulating factor but not to interferon-gamma, stem cell factor, tumor necrosis factor alpha, or IL-4. Interestingly, priming of chemoattractant-induced ERK activation is accompanied by an increase in association of tyrosine-phosphorylated proteins with the adapter protein Grb2. The biological relevance of ERK activation to IL-5 priming is supported by the observation that inhibition of ERK activity by treatment with the MEK inhibitors PD98059 or U0126 inhibited the release of leukotriene C(4) stimulated by fMet-Leu-Phe in IL-5-primed eosinophils. These data provide evidence for a previously undescribed fundamental mechanism by which stimulation of IL-5 family receptors induces a rapid phenotypic alteration in the signal transduction pathways of chemotactic receptors, enabling their activation of the ERK1 and ERK2 pathway and contributing to the capacity of these cells to synthesize LTC(4).
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PMID:ERK1 and ERK2 activation by chemotactic factors in human eosinophils is interleukin 5-dependent and contributes to leukotriene C(4) biosynthesis. 1075 97

Stem cell trafficking between extravascular marrow sites and circulating blood is an essential part of the blood stem cell transplantation technology. Recombinant human G-CSF (rHuG-CSF) is widely used for stem cell peripheralization alone or together with chemopriming mobilizing early and pluripotent CD34+ cell subsets. New cytokine/chemokine mobilization regimens are under investigation such as combined rHuG-CSF and rHu thrombopoietin, rHuG-CSF and interleukin 3, rHuG-CSF and rHu stem cell factor, rHuG-CSF and Flt-3 ligand, human macrophage inflammatory protein, interleukin 1, and interleukin 8. Modifying the adherence of CD34+ cells to extracellular matrix molecules is a new mechanism by which hematopoietic progenitor cells are released into the circulating blood. Blocking the alpha4beta1 integrin receptor on CD34+ progenitor cells by using monoclonal antibodies specific for the heterodimeric complex alpha4beta1 has been shown to further increase the circulating stem cell concentration when given following rHuG-CSF priming. The current clinical research is primarily focused on improving stem cell mobilization efficiency in heavily pretreated and poorly mobilizing patients, and to decrease adverse effects of cytokine treatment.
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PMID:In vivo expansion of the circulating stem cell pool. 1101 55

Paclitaxel and carboplatin chemotherapy is reported to be a platelet-sparing drug combination. This study investigated potential mechanisms for this observation by studying the effects of paclitaxel and carboplatin on (1) normal donor and chemotherapy patient-derived erythroid (burst-forming units-erythroid [BFU-E]), myeloid (colony-forming units-granulocyte/macrophage [CFU-GM]), and megakaryocyte (CFU-Meg) progenitor cell growth; (2) P-glycoprotein (P-gp) protein and glutathione S-transferase (GST) messenger RNA (mRNA) expression; (3) serum thrombopoietin (Tpo), stem cell factor (SCF), interleukin-6 (IL-6), IL-11, IL-1beta, IL-8, and tumor necrosis factor-alpha levels in patients treated with paclitaxel and carboplatin; and (4) stromal cell production of Tpo and SCF after paclitaxel and carboplatin exposure. CFU-Meg were more resistant to paclitaxel alone, or in combination with carboplatin, than CFU-GM and BFU-E. Although all progenitors expressed P-gp protein and GST mRNA, verapamil treatment significantly, and selectively, increased the toxicity of paclitaxel and carboplatin to CFU-Meg, suggesting an important role for P-gp in megakaryocyte drug resistance. Compared to normal controls, serum Tpo levels in patients receiving paclitaxel and carboplatin were significantly elevated 5 hours after infusion and remained elevated at day 7 (287% +/- 63% increase, P <.001). Marrow stroma was shown to be the likely source of this Tpo. It is concluded here that P-gp-mediated efflux of paclitaxel, and perhaps GST-mediated detoxification of carboplatin, results in relative sparing of CFU-Meg, which may then respond to locally high levels of stromal cell-derived Tpo. The confluence of these events might lead to the platelet-sparing phenomenon observed in patients treated with paclitaxel and carboplatin chemotherapy.
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PMID:Investigating the platelet-sparing mechanism of paclitaxel/carboplatin combination chemotherapy. 1115 79

Mature human mast cells are tissue-residing, key effector cells of immediate allergic reactions. Moreover, mast cells have been recognized as a potent cellular source of multiple cytokines, suggesting an important role in immunoregulation and host defense. Here, we report on the regulation of mature human mast cells isolated from intestinal tissues by stem cell factor (SCF) and interleukin (IL)-4. SCF is substantially necessary for mast cell survival and induces marginal mast cell proliferation in vitro, whereas IL-4 by itself has no effects on mast cell survival or proliferation. Most interestingly, in synergy with SCF, IL-4 strongly enhances mast cell proliferation. In the presence of SCF, mast cells predominantly produce pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, IL-16, and IL-18. Addition of IL-4 to the culture medium induces the expression of Th2-type cytokines (IL-3, IL-5 and IL-13), and a downregulation of pro-inflammatory cytokines, namely IL-6. Furthermore, SCF by itself supports the predominance of the tryptase/chymase double-positive mast cell subtype MCTC whereas the addition of IL-4 supports the chymase negative MCT subtype. In conclusion, SCF may primarily regulate resident mast cell survival, whereas IL-4 may promote local proliferation of mast cells and their expression of Th2-type cytokines.
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PMID:Regulation of human intestinal mast cells by stem cell factor and IL-4. 1129 28

Angiogenesis is tightly regulated by pro- and anti-angiogenic factors. Secreting mast cells are able to induce and enhance angiogenesis via multiple in part interacting pathways. They include mast cell-derived (i) potent pro-angiogenic factors such as VEGF, bFGF, TGF-beta, TNF-alpha and IL-8, (ii) proteinases and heparin, that release heparin-binding pro-angiogenic factors lodged on cell surfaces and in the extracellular matrix (ECM), (iii) histamine, VEGF, and certain lipid-derived mediators that induce microvascular hyperpermeability having pro-angiogenic effects, (iv) chemotactic recruitment of monocytes/macrophages and lymphocytes that are able to contribute with angiogenesis-modulating molecules, (v) activation of platelets that release pro-angiogenic factors, (vi) activation of neighboring stationary non-mast cells, which secrete pro-angiogenic factors, ECM-degrading proteinases and stem cell factor which attracts, mitogenically stimulates and activates mast cells, (vii) auto- and paracrine stimulation of mast cells by stem cell factor, (viii) recruitment of mast cells by pro-angiogenic factors such as VEGF, bFGF and TGF-beta. As a result of ECM-degradation and changes in the microenvironment following initial mast cell secretion, the mast cell populations may change significantly in number, phenotype and function. In tumor models, mast cells have been shown to play a decisive role in inducing the angiogenic switch which precedes malignant transformation. There is, moreover, strong evidence that mast cells significantly influence angiogenesis and thus growth and progression in human cancers.
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PMID:Mast cells and angiogenesis. 1207 53

The HMC-1 mast cell line has both adenosine A(3) and A(2b) receptors on its surface, but only agonists of the A(2b) receptor are effective at releasing interleukin 8. Object of this study was to look for co-factors for adenosine A(2b) receptor activation. There was a powerful and statistically significant synergy for release of IL-8, both at the mRNA level (measured after 4 hr) and protein level (measured after 24 hr), between adenosine A(2b) receptor agonists and stem cell factor (SCF). Suitable concentrations for showing synergy were 100 ng/mL SCF and 3 microM 5'-N-ethylcarboxamidoadenosine (NECA). At these concentrations, the IL-8 released into the culture medium after SCF and NECA together was typically 3-5-fold greater in amount than the sum of the amounts of IL-8 released after exposure to the same concentrations of NECA and SCF separately. Since mast cells may be exposed to both adenosine and stem cell factor in the diseased lung, the synergy observed in this model system may have implications for asthma.
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PMID:Induction of interleukin 8 release from the HMC-1 mast cell line: synergy between stem cell factor and activators of the adenosine A(2b) receptor. 1212 53

We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%, respectively, at an optimal concentration) but not by anti-stem cell factor, anti-TNF-alpha, or anti-IFN-gamma neutralizing Abs or by the antihistamine drugs pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD 98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8 release. Tryptase caused phosphorylation of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot). Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA). Eosinophils were found to express proteinase-activated receptor 2 (FACS). When eosinophils were incubated with tryptase in the presence of anti-proteinase-activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8 release occurred. In summary, we have demonstrated that the preformed mast cell mediator tryptase induces cytokine production and release in human peripheral blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.
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PMID:Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release. 1219 39


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