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

We characterized the immunophenotype as well as functional properties--phagocytosis, the uptake of acetylated LDL, and the expression of HLA class II antigens, adhesion molecules, and cytokine mRNA--of fibroblast-like synoviocytes from rheumatoid arthritis synovium. Skin fibroblasts (FB) and umbilical vein endothelial cells (HUVEC) were studied in parallel. Cytofluorometric immunophenotyping by use of 84 mAb and 2 lectins and immunofluorescence microscopy indicated a high degree of homology between the three cell types. Only staining with mAb to von Willebrand factor (vWF) and CD31 and the lectin UEA-I appeared specific to HUVEC, whereas the mAb 5B5 to prolyl 4-hydroxylase that has been reported to be specific to FB stained HUVEC as well as synoviocytes and FB. All of the cells phagocytosed fluorescent latex beads of 1.7 and 2.6 microns in size. The uptake of acetylated LDL could be shown by HUVEC and, surprisingly, by synoviocytes, but not by FB. The induction of HLA-DR, -DP, and -DQ by IFN-gamma on the three cell types showed a similar dose-dependence. The upregulation of ICAM-1 by IL-1 alpha, TNF-alpha, and IFN-gamma appeared similar, whereas the induction of VCAM-1 by IL-1 alpha, IL-4, TNF-alpha, and IFN-gamma showed differences between the three cell types. ELAM-1 was expressed only on HUVEC after treatment with IL-1 alpha and TNF-alpha. The capacity of the cells to produce cytokines was studied at the level of mRNA by reverse transcription and PCR. All three cell types expressed the mRNA of IL-1 alpha, IL-6, IL-8, GM-CSF, and TGF-beta 1 spontaneously or after LPS stimulation, but never TNF-alpha mRNA. Our results indicate a high degree of relationship between the three cell types. In contrast to HUVEC, none of the markers and functional properties investigated appear specific to FB. Therefore, the issue of the origin of fibroblast-like synoviocytes and the role of vascular endothelial cells in the inflamed synovium is discussed.
 ...
PMID:Characterization of the immunophenotype and functional properties of fibroblast-like synoviocytes in comparison to skin fibroblasts and umbilical vein endothelial cells. 808 88

Hematopoiesis is regulated by colony-stimulating factors (CSF) and many other cytokines. T helper cell and monocyte/macrophage interactions that take place in the immune response, resulting in the production of many cytokines, probably can influence inducible hematopoiesis. We investigated the effect of the T helper cell-derived lymphokines IL-2, IL-3, GM-CSF, and IFN-gamma, on the expression of cytokine genes in monocytes and compared this to LPS-induced cytokine gene expression in monocytes. To avoid inadvertent activation of monocytes, cells were purified by elutriation and cultured under serum-free, LPS-free, and nonadherent conditions. Similar to LPS, IL-2, IL-3, and GM-CSF induced the expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and IL-1-RA genes in monocytes, but with some differences in the amount and kinetics of cytokine mRNA accumulation. Unlike LPS, IL-2, IL-3, and GM-CSF did not induce G-CSF and GM-CSF gene expression in monocytes. GM-CSF and IL-3 were the only inducers capable of expressing the M-CSF gene in monocytes. IL-2, IL-3, and GM-CSF showed no effect on the IL-10 gene while IFN-gamma appeared to have no effect on any of the cytokine genes studied in monocytes. These data indicate that in the immune response expression of the proinflammatory cytokine genes, IL-1 beta, IL-6, IL-8, and TNF-alpha, can occur and that autoregulatory control mechanisms, like the expression of IL-1-RA gene, are also activated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulatory effects of T cell lymphokines on cytokine gene expression in monocytes. 812 62

Paraquat (PQ) is a herbicide which is highly pneumotoxic by generating reactive oxygen intermediates (ROI). Pro-inflammatory cytokines, particularly IL-1 and TNF, have been implicated in some ROI-mediated pathologies, including bleomycin toxicity and ischaemia/reperfusion injury. We have studied the effect of PQ on the expression of the neutrophil chemotactic cytokine, IL-8, by human peripheral blood mononuclear cells (PBMC). While almost no IL-8 mRNA was detected in unstimulated cells, PQ (100 microM) induced high mRNA expression with a maximum at 24 h of incubation. While PQ did stimulate the appearance of IL-8 mRNA, no significant production of IL-8 protein was detected. However, PQ potentiated the production of IL-8 in the presence of 1 ng/ml of endotoxin (lipopolysaccharide, LPS). This was paralleled by an increased production of chemotactic activity for neutrophils, indicating that the IL-8 was actually bioactive. Stimulation of IL-8 mRNA by PQ was suppressed by IL-4 and by free radical scavengers (dimethylsulfoxide, mannitol). Increased IL-8 expression by PQ was also observed in the human pulmonary epithelial cell line A549 indicating that the effect of PQ was not specific for PBMC. These findings suggest that IL-8 might be involved in the pulmonary effects of PQ and that its production might be stimulated following an oxidative insult, and might clarify the pathogenetic mechanisms of adult respiratory distress syndrome (ARDS) or oxidant-induced pulmonary fibrosis.
 ...
PMID:The pneumotoxicant paraquat induces IL-8 mRNA in human mononuclear cells and pulmonary epithelial cells. 814 10

In this study, we examined IL-10 regulation of polymorphonuclear leukocyte (PMN)-derived chemokine expression. Studies demonstrated that IL-10 dose dependently suppressed the expression and production of PMN-derived macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, IL-8 mRNA, and protein. Although inhibition of protein synthesis was found to superinduce the expression of PMN-derived chemokine steady-state mRNA, the inhibitory activity of IL-10 was completely abrogated in the presence of either cycloheximide or puromycin. These data suggest that the effect of IL-10 on PMN-derived chemokine expression was through the production of de novo repressor protein(s). Next, we examined the half-life (t1/2) of chemokine mRNA by LPS-treated PMNs in the presence or absence of IL-10. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated for 4 h with LPS before actinomycin-D (Ac-D) addition were approximately 40 min, 1.7 h, and 2 h, respectively, whereas the t1/2 from PMNs stimulated for 8 h before Ac-D were 2, 2, and > 9 h, respectively. Interestingly, IL-10 significantly accelerated the decay of all three of the above chemokine mRNA. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated with LPS plus IL-10 compared with LPS alone was reduced by 62, 50, and 40%, respectively, at the 4-h time point and by 50, 25, and 70%, respectively, at the 8-h time point. These findings support the notion that PMNs are an important cellular source of both C-X-C and C-C chemokines, and that IL-10 regulates both inflammatory/immune responses by not only modulating the activities of T cell, B cell, and mononuclear phagocyte function, but also by inhibiting PMN-derived chemokine expression.
 ...
PMID:Regulation of neutrophil-derived chemokine expression by IL-10. 814 35

Recently, "low-dose and long-term" erythromycin (EM) has been reported to be effective in treatment of diffuse panbronchiolitis (DPB), but its mechanism is still obscure. We studied the effect of EM on cytokine mRNA expression by using LPS-stimulated human whole blood as an experimental vivo model. IL-8 mRNA was expressed in biphasic fashion with peak expression at 6 hours and 20 hours from the start of LPS stimulation. When whole blood was pretreated with EM (2 micrograms/ml) for 1 hours. IL-8 mRNA expression was depressed at 20 hours (p < 0.025) from the start of LPS (1 microgram/ml) stimulation. However, when pretreated for 12 hours, it was not depressed. EM (2 micrograms/ml) also depressed IL-1 beta (p < 0.025) and TNF alpha (p < 0.05) mRNA expressions at 6 hours from the start of LPS stimulation. From the above results, it was suggested that the direct inhibition of IL-1 beta and TNF alpha production by EM resulted in subsequent depression of production of IL-8 that is a potent chemotactic factor for neutrophil, and consequently, EM acts to protect the bronchiole tissues of DPB patients from destruction by proteolytic enzymes released from neutrophils. This assumption seems to be supported by our previous observation that when patients with DPB were treated with EM a marked decrease in number of neutrophil in bronchoalveolar lavage fluid (BALF) was accompanied by clinical and radiographic improvement.
 ...
PMID:[Mechanism of efficacy of erythromycin on diffuse panbronchiolitis--effect of erythromycin on cytokine mRNA expression in human whole blood model]. 815 Nov 47

Interleukin-1 receptor antagonist (IL-1ra) has the potential to counteract at least part of the biological effects of interleukin-1. The outcome of an inflammatory reaction may therefore be determined by the balance between IL-1 and IL-1ra, rather than by IL-1 alone. We have developed an immunoassay to address this issue as well as to assess the effects of anti-inflammatory agents on the expression of IL-1 and IL-1ra in vitro or in body fluids. Recombinant human IL-1ra was expressed in an E. coli system, purified to homogeneity, and used to derive monoclonal antibodies in mice as well as polyclonal antibodies in rabbits. A sandwich ELISA was constructed with F(ab')2 fragments of a high affinity monoclonal antibody and the rabbit serum as a source of secondary antibody. The assay required no sample treatment to avoid interference by rheumatoid factor. The measuring range was 0.020-2 ng/ml. By labelling a second monoclonal antibody with an acridinium ester, a chemiluminescence assay with a wider measuring range (0.050-15 ng/ml) was generated. In accord with published data, we found that IL-1ra was secreted by human monocytes stimulated with LPS, Zymosan, IL-1 alpha, or human IgG. After an induction phase of ca. 4 hours and depending on the stimulus, IL-1ra accumulated linearly for periods up to 96 h. IL-1ra levels in synovial fluids of 19 patients suffering from various inflammatory joint diseases were compared with the cytokine levels of IL-1 beta, IL-6, IL-8, and TNF-alpha. Highest positive correlations were found with IL-8 and IL-1 beta. In normal blood donors IL-1ra serum levels were 150-800 pg/ml (Median: 387 pg/ml). Owing to its sensitivity and large measuring range the newly developed assays appear to be suitable for measuring IL-1ra in cell cultures as well as in biological fluids.
 ...
PMID:Monoclonal antibody based enzyme-linked and chemiluminescent assays for the human interleukin-1 receptor antagonist. Application to measure hIL-1ra levels in monocyte cultures and synovial fluids. 815 85

Antibiotic-induced endotoxin (lipopolysaccharide; LPS) release may precipitate septic shock. In the present study the effect of teicoplanin, which has been reported to neutralize LPS in experimental models, on LPS neutralization was investigated in human whole blood samples. Levels of interleukin 8, a preinflammatory cytokine which was stimulated by Salmonella minnesota R595 LPS (12.6 micrograms/ml), were monitored over time. Interleukin 8 concentrations increased over time up to 24 h. When LPS was preincubated with teicoplanin (antibiotic: LPS ratio 20:1, w/w), interleukin 8 concentrations were found significantly (p < 0.05) reduced at 4, 8 and 24 h after LPS challenge. Interleukin 1 beta (at 4, 8 and 24 h) and tumor necrosis factor alpha (at 8 and 24 h) levels were also significantly decreased by teicoplanin. In this experiment model, a teicoplanin:LPS ratio 100-fold less than the ratio achievable in plasma of septic shock patients was able to reduce interleukin 8, which has been correlated with the severity of septic disease.
 ...
PMID:Inhibition of endotoxin-induced interleukin 8 release by teicoplanin in human whole blood. 818 90

The temporal recruitment of leukocytes to a site of inflammation is dependent on a complex interplay of a number of soluble mediators. Recently, two families of chemotactic cytokines have been discovered. The -C-X-C-family, which includes IL-8, appears to recruit neutrophils and lymphocytes. In contrast, the -C-C-family, which includes monocyte chemotactic peptide-1 (MCP-1), appears to recruit predominantly monocytes. Monocytes, after their arrival at a site of inflammation, could further amplify the immune response by secreting IL-8 and MCP-1. We sought to define conditions under which human peripheral blood monocytes produce IL-8 and MCP-1. Using serum-free media, we found that PHA-stimulated monocytes expressed MCP-1 and IL-8 protein and mRNA in a dose-dependent manner. However, the onset of mRNA expression for MCP-1 occurred at least 3 h later than did the onset of IL-8 mRNA expression. IL-8 and MCP-1 gene expression by monocytes appeared to require de novo protein synthesis, in that cycloheximide blocked the expression of mRNA for both IL-8 and MCP-1 in PHA-stimulated cells. However, treatment of monocytes with cycloheximide resulted in the superinduction of IL-8 compared with control monocytes. Monocytes costimulated with PHA and LPS demonstrated enhanced amounts of IL-8 mRNA and protein, but sharply decreased amounts of MCP-1 mRNA and protein. The addition of serum to culture media increased both the constitutive and PHA-induced production of monocyte-derived MCP-1 and IL-8, but had no effect on the inhibition of PHA-stimulated MCP-1 production by LPS. These findings suggest that distinct pathways of activation exist for the production of monocyte-derived IL-8 and MCP-1. The differential expression of these different but related polypeptides may offer a means of control of the type of immune cells that are recruited to a site of inflammation.
 ...
PMID:Production of IL-8 and monocyte chemotactic peptide-1 by peripheral blood monocytes. Disparate responses to phytohemagglutinin and lipopolysaccharide. 825 94

ETH615 (4-[2-quinolylmethoxy]-N-[3-fluorobenzyl]-phenylaminometh yl-4-benzoic acid) is a potent inhibitor of leukotriene biosynthesis in A23187-stimulated leukocytes, and of IL-8 gene expression in LPS-stimulated PBMC. It shows anti-inflammatory activity in a canine model of dermal inflammation. A topical formulation is present in phase II clinical trials. In the present study the effect of ETH615 on oxazolone-induced acute inflammation and phorbol ester-induced chronic inflammation in the mouse ear was investigated. Betamethasone (0.04 mg/ear) and ETH615 (1-1.5 mg/ear) significantly inhibited both the oedema formation and the PMN infiltration. The cream and ointment formulations of ETH615 developed for clinical studies were equally active. ETH615 is thus an anti-inflammatory agent in these murine models of dermatosis.
 ...
PMID:Effect of ETH615, an inhibitor of leukotriene synthesis and IL-8 gene expression, on murine dermatoses. 827 57

Cryptococcus neoformans, a pathogenic fungus usually acquired by inhalation, causes the most common lethal mycosis in AIDS. The resident lung phagocytes, alveolar macrophages (AM phi), inhibit growth of C. neoformans poorly unless activated by cytokines such as IFN-gamma. In this study, we examined the effect of rat AM phi of the potent hematopoietic and M phi-activating cytokine, granulocyte-macrophage CSF (GM-CSF), alone and in combination with other cytokines. Rat AM phi monolayers were preincubated with 0.1 to 1000 U/ml GM-CSF without or with other recombinant cytokines, and then were incubated with viable C. neoformans (strain H99/C3D). Growth inhibition was assessed by counting cryptococcal CFU at 24 and 48 h of coculture; AM phi proliferation was assessed by measuring both uptake of [3H]TdR and AM phi numbers. AM phi preincubated with GM-CSF for 5 days (but not for shorter periods) inhibited growth of C. neoformans. Anticryptococcal activity required direct contact of AM phi with C. neoformans, but once induced by preincubation, did not require continued exposure to GM-CSF. Induction of anticryptococcal activity by GM-CSF was dose dependent (maximal induction at 250 U/ml), and was due to both increased ingestion and killing. GM-CSF induced AM phi proliferation, but anticryptococcal activity was not due totally to increases in AM phi numbers, indicating AM phi activation by GM-CSF. GM-CSF-induced AM phi proliferation was increased by IL-6, unchanged by IL-8, and abolished by LPS or IFN-gamma. However, IL-6 did not increase GM-CSF-induced anticryptococal activity. The combination of GM-CSF and IFN-gamma showed rapid and sustained anticryptococcal activity, unlike either cytokine alone. Our in vitro data suggest that the combination of GM-CSF and IFN-gamma may have beneficial effects on host defense against C. neoformans in vivo.
 ...
PMID:Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro. 828 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>