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)

High-density lipoprotein (HDL) has been found to neutralize LPS activity in vitro and in animals in vivo. We sought to determine the effects of reconstituted HDL (rHDL) on LPS responsiveness in humans in a double-blind, randomized, placebo-controlled, cross-over study. rHDL, given as a 4-h infusion at 40 mg/kg starting 3.5 h before endotoxin challenge (4 ng/kg), reduced flu-like symptoms during endotoxemia, but did not influence the febrile response. rHDL potently reduced the endotoxin-induced release of TNF, IL-6, and IL-8, while only modestly attenuating the secretion of proinflammatory cytokine inhibitors IL-1ra, soluble TNF receptors and IL-10. In addition, rHDL attenuated LPS-induced changes in leukocyte counts and the enhanced expression of CD11b/CD18 on granulocytes. Importantly, rHDL infusion per se, before LPS administration, was associated with a downregulation of CD14, the main LPS receptor, on monocytes. This effect was biologically relevant, since monocytes isolated from rHDL-treated whole blood showed reduced expression of CD14 and diminished TNF production upon stimulation with LPS. These results suggest that rHDL may inhibit LPS effects in humans in vivo not only by binding and neutralizing LPS but also by reducing CD14 expression on monocytes.
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PMID:Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. 892 Aug 50

Ehrlichia chaffeensis is a recently isolated minute gram-negative obligatory intracellular bacterium of monocytes/macrophages and is the etiologic agent of human monocytic ehrlichiosis. It is not known how macrophages respond when they encounter ehrlichiae in terms of cytokine production. In this study, we examined cytokine mRNA expression by incubating E. chaffeensis with THP-1 cells and performing competitive reverse transcription-PCR (RT-PCR). At 2 h postinfection, the levels of interleukin-1beta (IL-1beta), IL-8, and IL-10 mRNAs were significant but lower than those following Escherichia coli lipopolysaccharide (LPS) stimulation. Unlike the situation with E. coli LPS stimulation, however, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha) mRNAs were not induced. Time course and dose-response studies confirmed the absence of IL-6, GM-CSF, and TNF-alpha mRNA induction with E. chaffeensis. Viable E. chaffeensis organisms were not required for IL-1beta IO, IL-8, and IL-10 mRNA induction, since heat-killed E. chaffeensis induced identical time course responses. IL-1beta, IL-8, and IL-10 mRNAs were detected for up to 21, 21, and 24 h postexposure with E. chaffeensis, respectively, which were shut off more rapidly than with LPS stimulation. Although heat treatment of E. chaffeensis had no effect, periodate treatment completely abolished the ability of E. chaffeensis to induce IL-1beta, IL-8, and IL-10 mRNAs. The capture enzyme-linked immunosorbent assay result corresponded with the RT-PCR results, showing that viable and heat-killed E. chaffeensis produced and secreted the same levels of IL-1beta and IL-8. IL-10 production was significantly reduced by heat treatment. Periodate-treated ehrlichiae did not induce production of any of the cytokines tested. Anti-CD14 monoclonal antibody and polymyxin B did not inhibit IL-1beta mRNA expression upon exposure to E. chaffeensis. The absence of TNF-alpha, IL-6, and GM-CSF mRNA induction may delay the development of a protective immune response, thereby allowing E. chaffeensis to set up residence in macrophages.
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PMID:Absence of tumor necrosis factor alpha, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor expression but presence of IL-1beta, IL-8, and IL-10 expression in human monocytes exposed to viable or killed Ehrlichia chaffeensis. 892 90

In the mouse, mutations at the natural resistance-associated macrophage protein 1 (Nramp1) gene abrogate resistance to infection with antigenically unrelated intracellular parasites such as Mycobacterium, Salmonella, and Leishmania. Nramp1 expression is restricted to reticuloendothelial organs and peripheral blood leukocytes, where the protein may function as a membrane transporter of an as yet to be identified substrate. To identify the human blood cell type(s) expressing NRAMP1 mRNA and determine how Nramp1 expression is regulated in these cells, we have examined separated populations of peripheral blood leukocytes and in vitro cell lines. We observed that polymorphonuclear leukocytes (PMN) are the major site of NRAMP1 expression, followed to a lesser degree by monocytes (MN). Migration of MN to tissues (alveolar macrophages) or maturation in vitro (long-term culture) was associated with a higher level of NRAMP1 expression compared with blood MN. Northern analyses of RNA from model cultured cells showed absence of NRAMP1 expression in transformed cell lines from either erythroid or lymphoid T or B lineages as well as progenitors of the monocyte/macrophage pathway (KG1, U937, THP1), and the HL-60 promyelocytic leukemia. Induction of differentiation of HL-60 cells toward either the monocyte/macrophage (vitamin D3, phorbol ester) or the granulocyte pathways (DMF, DMSO), as measured by induction of IL8-Rb, c-FMS, and CD14 marker gene expression, was concomitant with a strong induction of NRAMP1 expression. These results suggest that NRAMP1 expression is specific to the myeloid lineage and is acquired during the maturation of PMN and MN. The possibility that NRAMP1 may be a component of the phagosomal/endosomal apparatus common to PMN and MN is discussed.
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PMID:Expression of the human NRAMP1 gene in professional primary phagocytes: studies in blood cells and in HL-60 promyelocytic leukemia. 900 May 42

To investigate the responses of dendritic cells (DC) during Gram-negative infections, we analyzed the effects of graded doses of LPS on the cytokine profile, phenotype, and allostimulatory potential of human DC generated by culturing plastic-adherent PBMC in presence of IL-4 and granulocyte-macrophage-CSF. First, we found that LPS stimulates the production of high levels of TNF-alpha, IL-6, IL-8, IL-12 by DC and up-regulates their expression of HLA-DR, B7-1, B7-2, and CD40. The effects of LPS were dose dependent, with a significant stimulatory effect already observed at a concentration of 0.1 ng/ml and a plateau being reached at 10 ng/ml. These phenotypic changes correlated with increased allostimulatory properties of LPS-activated DC because DC treated with LPS were significantly more efficient than untreated DC in eliciting IL-2 and IFN-gamma synthesis by alloreactive T cells and stimulating their proliferation. Experiments using neutralizing anti-IL-12 mAb indicated that LPS-induced IL-12 is responsible for the increased production of IFN-gamma but not for the increased proliferation during MLR. Finally, we observed that the DC responses to low levels of LPS (1 ng/ml) were dramatically inhibited by a blocking anti-CD14 mAb, although DC do not express CD14 molecules on their membrane. Experiments using serum depleted of soluble CD14 (sCD14) and sCD14 either purified from human serum or in recombinant form further established that DC respond to LPS via a soluble CD14-dependent pathway.
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PMID:Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. 905 30

We evaluated the effects of interleukin (IL)-10 on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells for 7 days in presence of granulocyte/macrophage-colony-stimulating factor (GM-CSF) + IL-4. The addition of IL-10 at the initiation of culture resulted in the generation of macrophage-like cells with expressing high levels of CD14 and decreased levels of CD1a and CD1c. Furthermore, cells generated in presence of IL-10 secreted lower levels of IL-12, but higher levels of IL-8 compared with DC generated in absence of IL-10, both spontaneously and after CD40 engagement. Finally, cells generated in presence of IL-10 were less efficient than DC in stimulating the production of IL-2, interferon-gamma, and IL-4 by allogeneic T cells. We conclude that IL-10 prevents the generation of DC induced by GM-CSF + IL-4 and favors the development of macrophages with a lower T cell stimulatory potential, but secreting higher levels of IL-8 than DC.
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PMID:Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. 907 19

We describe a 15-yr-old girl with recurrent bacterial infections who is refractory to the effects of LPS in vivo and in vitro and IL-1 in vitro. Intravenous challenge of the patient with Escherichia coli endotoxin caused a subnormal febrile response, little alteration in the number of circulating neutrophils, and subnormal elevations in the plasma levels of TNF-alpha, IL-6, IL-8, lactoferrin, and granulocyte CSF; however, normal levels of the anti-inflammatory mediators IL-1 receptor antagonist and soluble TNF receptor (60 kDa) were induced. Studies in vitro indicated the patient's monocytes expressed CD14, the LPS receptor, and bound LPS in a specific manner, but failed to produce TNF-alpha and granulocyte CSF after stimulation with LPS, and failed to respond to IL-1, heat-killed Staphylococcus aureus, and soluble glucan. Peripheral blood patient neutrophils exhibited normal expression of CD14, but failed to respond to treatment with LPS (100-1000 ng/ml for 30 min at 37 degrees C), a treatment that caused increased expression of the surface markers, C10, CD18, CD11b, CD67, and CD45, and decreased expression of L-selectin in normal neutrophils. Treatment of normal and patient neutrophils with FMLP (0.1 microM) resulted in equivalent altered expression of these surface markers. Patient neutrophils could not be primed by either LPS or IL-1beta for enhanced FMLP-induced O2- generation, but primed normally to TNF-alpha and platelet-activating factor. This patient's hyporesponsiveness to LPS and IL-1 is most likely due to a defect very early in the signal-transduction pathway.
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PMID:Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections. 910 66

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.
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PMID:TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. 912 3

The accumulation of sCD14 shed from human monocytes in vivo might correlate with other inflammatory parameters and could be of importance in overcoming a sepsis situation. The development of the sCD14 titer in the supernatant of monocyte-enriched MNC cultures isolated from healthy volunteers was studied utilizing a commercially available sCD14 ELISA. These culture experiments revealed the prolonged liberation of sCD14 into the supernatant during a period of several days. A medium-exchange schedule of 2-3 days was found to be superior to a longer incubation period with respect to the sCD14 yield. PMA initially enhanced the CD14 shedding slightly, but after a few hours it strongly repressed the process. Such a reduction was also achieved by protein synthesis inhibitors (cycloheximide, actinomycin D). Additionally, we monitored the concentration of sCD14, CRP, IL-6 and IL-8 in human sera from healthy persons or patients suffering from severe burn injuries with or without sepsis. Our results indicate that sCD14 is strongly correlated with IL-6, but not with IL-8. sCD14 titers were higher in the group of patients with both burn injuries and sepsis. From experiments with monocyte-enriched MNC cultures isolated from healthy volunteers and medium supplemented with sera containing sCD14 as well as radiolabeled LPS, we conclude that the enhanced shedding of CD14 in vivo during sepsis is probably not able to reduce the binding of LPS to monocytes.
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PMID:Characteristics of CD14 shedding from human monocytes. Evidence for the competition of soluble CD14 (sCD14) with CD14 receptors for lipopolysaccharide (LPS) binding. 926 97

Human monocytes express functional IL-2Rs and are directly activated by IL-2 to exert effector and secretory functions. In this study, we demonstrate that the myeloid differentiation Ag CD14 participates in monocyte activation by IL-2. Engagement of CD14 by specific mAbs resulted in the selective and dose-dependent suppression of IL-2-induced, but not of IFN-gamma-induced, monocyte tumoricidal activity. Furthermore, anti-CD14 mAbs effectively inhibited the secretion of IL-8 and IL-1beta in response to IL-2. Preincubation of monocytes with mAbs directed to selected epitopes on CD14 blocked the binding of IL-2 to the cell surface, providing a possible explanation for the inhibition of IL-2-triggered responses. A critical role for CD14 in IL-2-mediated monocyte activation was further demonstrated by experiments with the human U937 promonocytic cell line. These cells are negative for CD14 and unresponsive to IL-2 despite the expression of the beta and gamma subunits of the IL-2R. U937 cells acquired the capacity to respond to IL-2 following transfection with the human CD14 cDNA (U937/CD14). Stimulation of U937/CD14 cells with IL-2 up-regulated the constitutive levels of IL-8 mRNA, whereas no change in IL-8 mRNA basal expression was observed in control cells transfected with the vector alone (U937/Neo). Accordingly, increased secretion of IL-8 by U937/CD14, but not by U937/Neo cells, was detected following exposure to IL-2. Expression of IL-1beta was also augmented by IL-2 in U937/CD14 cells. These data provide the first evidence that CD14 expression is required for the response of monocytic cells to IL-2.
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PMID:Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2. 930 Jul 16

Chronic inflammation induced by bacteria often leads to host-mediated destruction of tissues adjacent to the sites of microbial insult. The chronic inflammatory process of adult periodontitis results in the destruction of supporting osseous and connective tissues of the teeth. We hypothesized that virulence factors of periodontal pathogens such as lipopolysaccharide stimulate inflammatory cytokine expression by mononuclear cells of the host which contribute to disease development. In this study, to elucidate the role of these cytokines in chronic adult periodontitis, we tested whether the prevalence of mRNA for inflammatory cytokines generally associated with mononuclear phagocytes was higher in diseased than in healthy gingival tissue. Gingival mononuclear cells or whole gingival biopsies from 32 adult periodontitis patients and five healthy individuals used as controls were evaluated for inflammatory cytokine mRNA expression by reverse-transcription polymerase chain-reaction (RT-PCR) procedures. The cytokines assessed included IL-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, IL-12, IL-13, TNF-alpha, TGF-beta, and IFN-gamma. The monocyte/macrophage lipopolysaccharide (LPS) receptor CD14 was also assessed. Results showed that TNF-alpha mRNA was present significantly more frequently in diseased than in healthy biopsies, whereas IL-1 alpha, IL-1 beta, and IL-1ra mRNA were found in most (from 80 to 100%) healthy tissues. Message for CD14 was present in both healthy and diseased tissue samples (100%). This study provides evidence for a major role of TNF-alpha in chronic adult periodontitis. Moreover, our results suggest that the mononuclear cells derived from periodontal tissues have the capacity to respond to components of periodontal pathogens and express both pro- and anti-inflammatory cytokines in these tissues.
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PMID:Profile of cytokine mRNA expression in chronic adult periodontitis. 939 Apr 76

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