Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered polymorphonuclear leukocyte (PMN) function is thought to contribute to organ dysfunction during the systemic inflammatory response syndrome (SIRS). To test this hypothesis, we evaluated whole blood PMN function adherent to fibronectin or laminin in patients with mild or severe acute pancreatitis as a paradigm for sirs. Whole-blood PMN intracellular H2O2 production, expression of CD32w (Fc gamma R II), CD16 (Fc gamma R III), and phagocytosis were performed using dichlorofluorescein diacetate, fluorescein isothiocyanate-labeled anti-CD32w, CD16, and serum-opsonized fluorescent microspheres. Group I (n x 7) represents normal control individuals; group II (n x 11) represents patients with mild acute pancreatitis. Group III (n x 15) represents critically ill patients with severe acute pancreatitis. Adherence of PMN from groups I and II to matrix proteins resulted in a 5% to 20% increase in each PMN function assayed whereas adherence of PMN from group III to matrix proteins resulted in 50% to 75% increases in each PMN function assayed. Pertussis toxin, pentoxifylline, and dibutyryl cyclic adenosine monophosphate (cAMP) each reduced group I-II H2O2 production and phagocytosis. Pentoxifylline and dibutyryl cAMP but not pertussis toxin reduced group III H2O2 production. Both intracellular H2O2 and phagocytosis assays from group III but not groups I-II showed exaggerated upregulation when exposed to NaF (4 mmol/L). Anti-interleukin-6 reduced the increase in intracellular H2O2 production in group III patients and significantly altered the exaggerated oxidative response to NaF. Longitudinal studies of group III whole-blood PMN showed persistent upregulation of intracellular H2O2 production in those patients whose hospital courses were complicated by multiple system organ failure. These results demonstrate abnormal whole blood PMN function during the systemic inflammatory response syndrome in the presence of fibronectin, or laminin and that this is mediated in part via a pertussis toxin insensitive altered guanosine triphosphate-binding protein.
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PMID:Polymorphonuclear leukocyte dysregulation during the systemic inflammatory response syndrome. 811 41

The ability of dicatechol rooperol and esters to inhibit the production of cytokines in endotoxin-stimulated human alveolar macrophages, human blood monocyte/macrophages, histiocytic cell line U937, and rat alveolar macrophages was examined in vitro. Rooperol derivatives inhibited the production of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. Of the esters tested on human cells, rooperol diacetate and tetraacetate were more potent inhibitors of cytokine production (IC50 in the range of 10-20 microM) than rooperol disulphate (IC50 in the range of 25-75 microM). The acetate esters also inhibited cytokine production in rat alveolar macrophages, whereas the sulphate had little effect. Rooperol and acetate esters, in the same concentration range, decreased the production of nitric oxide by rat alveolar macrophages stimulated by endotoxin. These concentrations of rooperol had no effect on cell viability, as indicated by incorporation of 14C-labelled leucine into macrophage proteins and their content of lactate dehydrogenase. The results obtained suggest that rooperol esters are potentially useful antiinflammatory agents.
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PMID:Cytokine production in human and rat macrophages and dicatechol rooperol and esters. 883 17

Fluorescein isothiocyanate (FITC) was found to stain cytoplasmic granules of avian heterophilgranulocytes. In tissue sections, the fluorescent granulocytes were predominantly distributed adjacent to trabecular bones. The fluorescein stained granulocytes were abundant in synovial fluids of chickens with synovitis. A significant correlation was observed in the percent of fluorescein labeled granulocytes in blood smears and the percent of heterophils determined using an automated counting method, in unstained blood from normal and Escherichia coli-infected turkeys. The fluorescein-binding heterophils purified from chickens showed a time dependent increases in the oxidation of 2',7'-dichlorofluorescin diacetate (DCF-DA) and the reduction of nitroblue tetrazolium (NBT) which were indicative of changes in oxidative burst in response to phorbol 12-myristate 13-acetate (PMA), Salmonella typhimurium lipopolysaccharide (LPS), and zymosan A (ZA). These heterophil-activating agents, also, caused significant degranulation at 16 h post-treatment, as indicated by the loss fluorescence. There were microscopically visible alterations in the cell shapes and a decrease in the density of granules due to treatment with LPS, PMA or ZA. In addition, these cells also showed phagocytic response which was evident at 30 min of incubation with fluorescent latex particles. Both chicken and turkey heterophils produced interleukin-6 in vitro at 24 h in response to LPS but not to PMA, FMLP or ZA. The chicken heterophils showed spontaneous production of matrix metalloproteinases (MMP) which was significantly enhanced by treatment with LPS, PMA, and ZA; however, LPS appeared to be most effective in inducing MMP production. These results demonstrate that the functions of heterophils can be differentially regulated by different activating agents and the fluorescein binding property of these cells may be useful for their histochemical identification.
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PMID:Fluorescein isothiocyanate staining and characterization of avian heterophils. 965 33

Chronic myeloid leukemia (CML) is characterized by an increased proliferative activity of the leukemic progenitors that produce an elevated number of mature granulocytes. Nevertheless, cell cycle-active agents, even in very high doses, are alone unable to eradicate the leukemic clone, suggesting the presence of a rare subset of quiescent leukemic stem cells. To isolate such cells, we first used Hoechst 33342 and Pyronin Y staining to obtain viable G(0) and G(1)/S/G(2)/M fractions of CD34(+) cells by fluorescence-activated cell sorting (FACS) from 6 chronic-phase CML patients' samples and confirmed the quiescent and cycling status of the 2 fractions by demonstration of expected patterns of Ki-67 and D cyclin expression. Leukemic (Ph(+)/BCR-ABL(+)) cells with in vitro progenitor activity and capable of engrafting immunodeficient mice were identified in the directly isolated G(0) cells. Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that many leukemic CD34(+) G(0) cells also expressed BCR-ABL mRNA. CD34(+) from 8 CML patients were also labeled with carboxyfluorescein diacetate succinimidyl diester (CFSE) before being cultured (with and without added growth factors) to allow viable cells that had remained quiescent (ie, CFSE(+)) after 4 days to be retrieved by FACS. Leukemic progenitors were again detected in all quiescent populations isolated by this second strategy, including those exposed to a combination of flt3-ligand, Steel factor, interleukin-3, interleukin-6, and granulocyte colony-stimulating factor. These findings provide the first direct and definitive evidence of a deeply but reversibly quiescent subpopulation of leukemic cells in patients with CML with both in vitro and in vivo stem cell properties.
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PMID:Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. 1047 35

Recently, culture conditions that stimulate the proliferation of primitive hematopoietic cells defined by various phenotypic and functional endpoints in vitro have been identified. However, evidence that they support a high probability of self-renewal leading to a large net expansion in vitro of transplantable cells with lympho-myeloid repopulating ability has been more difficult to obtain. The present study was designed to investigate whether the low overall expansion of human repopulating hematopoietic cells seen in vitro reflects a selective unresponsiveness of these rare cells to the growth factors currently used to stimulate them or, alternatively, whether they do proliferate in vitro but lose engrafting potential. For this, we used a high-resolution procedure for tracking and reisolating cells as a function of their proliferation history based on the loss of cellular fluorescence after staining with (5- and 6-) carboxyfluorescein diacetate succinimidyl ester. The results show that the vast majority of long-term culture-initiating cells and in vivo lympho-myeloid competitive repopulating units present in 5-day suspension cultures initiated with CD34(+) human cord blood and fetal liver cells are the progeny of cells that have divided at least once in response to stimulation by interleukin-3, interleukin-6, granulocyte colony-stimulating factor, Steel factor, and Flt3-ligand. Thus, most human repopulating cells from these two sources are stimulated to undergo multiple divisions under currently used short-term suspension culture conditions and a proportion of these retain engraftment potential.
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PMID:Direct evidence for multiple self-renewal divisions of human in vivo repopulating hematopoietic cells in short-term culture. 1097 64

High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns) (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P </= 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappaB-associated and/ or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappaB-luciferase reporter cell line, exposure to PM(2.5) at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappaB-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM(2.5) and ultrafine carbon black particles. Studies here are the first to show NF-kappaB-related inflammatory and cytokine gene expression after inhalation of PM(2.5) and oxidant-dependent induction of NF-kappaB activity by PM(2.5) in pulmonary epithelial cells.
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PMID:Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. 1091 84

Inflammation-induced changes in serum protein profiles and the effects of such serum on a chicken macrophage cell line HD11 were studied to find whether the changes in serum affect cellular immunity. Four-week-old male broiler chickens were injected subcutaneously with either olive oil or 50% croton oil mixed in olive oil to induce inflammation. The birds were bled at 48h after injection, and serum protein profiles were compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric evaluation. At 48h post-injection the serum from croton oil-injected birds showed distinct changes in protein profiles characterized by a selective increase or decrease in levels of several serum proteins. The protein bands which showed increases had relative molecular weights (Mr) corresponding to 65kilo Daltons (kD), 42kD, and two or more proteins with Mr> or =200kD. The levels of serum albumin (49kD), and a 56kD protein were reduced in croton oil-injected birds. The modulating effects of such serum on HD11 cells were studied using bacterial lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) induced functional activation of these cells. The LPS-induced interleukin-6 (IL-6) production by HD11 cells was not affected by the presence of either olive oil-treated control or croton oil-treated inflammatory serum but nitrite production was enhanced by the inflammatory serum. Similarly, inflammatory serum also enhanced PMA-induced respiratory burst measured using dichlorofluorescein diacetate (DCF-DA) oxidation mediated by reactive oxygen intermediates. These results suggest that inflammatory serum can modulate macrophage function by influencing the production of reactive oxygen and nitrogen species which could affect their phagocytic and bactericidal activities.
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PMID:Inflammation-induced changes in serum modulate chicken macrophage function. 1145 76

A novel approach is used to study the proliferating behaviour of primitive haematopoietic cell populations in response to different stimuli. A mathematical model based on the average proportion of apoptotic, dividing and quiescent cells in primitive haematopoietic cell populations is developed to describe the mitotic history of 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester-labelled cells. The cell cycle distributions in different cytokine-supplemented cultures of primitive human and mouse bone marrow cells are determined and compared with those found in vivo. The results indicate that a combination of flt-3 ligand, Steel factor and interleukin-11 or hyper-interleukin-6 provide a level of mitogenic stimulation similar to that existing in vivo after a myeloablative radiation dose. The comparison of the cell cycle distribution obtained for different cultures of human bone marrow CD34(+)(45RA/71)(-) cells demonstrates that the addition of flt-3 ligand in these cultures decreases apoptosis significantly but does not reduce quiescence. In addition, in vivo and in vitro, it was found that more than 3 days of stimulation are required to recruit a maximum number of quiescent cells into active cell cycle. These kinetics of cell cycle activation are found to be similar to those identified for the haematopoietic stem cells compartment in the same cultures. This mathematical analysis provides a useful tool for the development of haematopoietic stem cell culture processes for clinical applications.
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PMID:Cell cycle distribution of primitive haematopoietic cells stimulated in vitro and in vivo. 1159 Nov 79

Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium.
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PMID:Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. 1178 29

Ovotransferrin (OTF) is an acute phase protein in chickens, serum levels of which increase in inflammation and infections. To understand the significance of OTF in inflammation, we studied its in vitro effects on HD11 cells, a macrophage cell line, and heterophils isolated from blood using a panel of variables indicative of cellular activation. These included the production of interleukin-6 (IL-6), nitrite, matrix metalloproteinase (MMP), oxidation of dichlorofluorescein diacetate for respiratory burst and the degranulation of heterophils by the loss of fluorescein isothiocyanate positive cytoplasmic granules. The results show that ovotransferrin stimulates the production of IL-6, nitrite and MMP by HD11 cells and augments phorbol ester-induced respiratory burst. Ovotransferrin stimulated heterophils to produce IL-6, and MMP, but failed to produce nitrite, enhanced respiratory burst activity and degranulation. These results suggest that ovotransferrin can modulate macrophage and heterophil functions in chickens.
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PMID:Effects of ovotransferrin on chicken macrophages and heterophil-granulocytes. 1237 20


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