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)

Most gene expression methods often involve cumbersome steps or use expensive facilities. Additionally, some of the techniques, such as cDNA biochip, cannot define the sub-population of tissue from which the amplified cDNA was made. Here we present a rapid and high throughput screening method for analyzing the pattern of gene expression of tumor-infiltrating lymphocyte (TIL), which can minimize manipulations in cloned DNA sequencing and in bioinformatics. The pattern of TIL gene expression was studied in one ovarian cancer and one liver cancer. Our results have demonstrated that TILs have three different gene expression profiles: the first set of genes is involved in cell proliferation and mitogenic stimulation, such as c-myc and IL-8, LD78, MIP-1beta, insulin-induced protein and AH-receptor; the second set of genes includes those involved in attachment of lymphocytes to endothelium and extravasation into tumor tissues such as P-selectin ligand and integrin; and the third set, which includes genes such as the perforin, FAS ligand and granzyme B, is related to cytotoxic function to tumor cells. The patterns of TIL gene expression obtained from two specimens are marginally different and can be used in explaining the basis of molecular mechanisms regulating cellular interactions and cytotoxicity.
 ...
PMID:Identification of mRNAs expressed in tumor-infiltrating lymphocytes by a strategy for rapid and high throughput screening. 1102 87

The role of P selectin in the accumulation of neutrophils at acute dermal inflammatory sites induced by chemoattractants, LTB4 and IL-8 was investigated in the mouse. A mouse P-selectin-human IgG chimera bound to mouse neutrophils in vitro in a calcium-dependent manner, as detected by flow cytometry. A rat monoclonal antibody (mAb) against mouse P-selectin, RB40.34 abolished P-selectin-IgG chimera binding to mouse neutrophils, but a control antibody did not. Intradermal injection of LTB4 at a dose of 100 ng/site caused neutrophil accumulation to increase by 3-4 fold, as detected by measuring myeloperoxidase activity. Neutrophil extravasation to perivascular tissue was detected by histochemical observation. The intravenous injection of RB40.34 or the specific LTB4 antagonist, SM-15178, at doses at 5 mg/kg attenuated the accumulation of neutrophils by 55.6% and 70.3%, respectively, but a control antibody showed no effect. Similarly, intradermal administration of IL-8 at a dose of 5 microg/site induced significant neutrophil migration into the interstitial tissue of the skin, as followed by measuring myeloperoxidase activity and histopathologic analysis. The intravenous injection of RB40.34 at a dose of 5 mg/kg reduced the neutrophil accumulation by 59.2% in contrast, a control antibody showed no effect. To our knowledge, this is the first direct demonstration that P-selectin plays a substantial role in LTB4- and IL-8-induced neutrophil accumulation in mouse skin.
 ...
PMID:Role of P-selectin in the migration of neutrophils to chemoattractant-induced cutaneous inflammation in mice. 1112 55

The aim of this work was the evaluation of serum and ascitic fluid levels of chemokines (IL-8, growth-regulated oncogene (Gro-alpha), and monocyte chemotactic protein-1 (MCP-1)), and of soluble adhesion molecules (P-selectin, E-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in patients with spontaneous bacterial peritonitis (SBP). These compounds were serially analysed in serum and ascitic fluid by ELISA in patients with SBP (n = 20), non-infected cirrhotic controls (n = 12), and healthy controls (n = 15). Infected and non-infected cirrhotic patients showed significantly higher serum levels of adhesion molecules. SBP was associated with significantly higher serum and ascitic fluid levels of IL-8, Gro-alpha and ICAM-1 and with ascitic fluid concentrations of MCP-1. Significantly elevated serum levels of both ICAM-1 and VCAM-1 were detected in patient non-survivors after SBP. Thus, higher ascitic fluid levels of chemokines could be implicated in the peritoneal infiltrate in patients with SBP. Prognostic significance can be attributed to serum levels of ICAM-1 and VCAM-1 in these patients.
 ...
PMID:Serial analysis of serum and ascitic fluid levels of soluble adhesion molecules and chemokines in patients with spontaneous bacterial peritonitis. 1116 98

During surgery, incision of the skin under aseptic conditions is performed. Despite the absence of noxious agents, an inflammatory response may be induced. We studied the local inflammatory response in human skin as a result of surgical intervention, under aseptic conditions. Elective standardized vascular surgery served as a model. A series of skin biopsies was taken from the wound edge at different time points after first incision. Biopsies, directly taken at first incision were considered to represent normal skin. Additional biopsies were taken at 30 min after the start of surgery and just before closure of the wound, maximally 270 min after surgery. Kinetics of recruitment of cells, expression of adhesion molecules and the presence of pro-inflammatory cytokines was studied. Granulocytes were observed at first at 30 min after incision of the skin and their number increased in time. This granulocyte infiltration is paralleled by E-selectin expression on endothelial cells, which also was observed at first at 30 min after surgery with a further increase in number in time. Incision of the skin did not change P-selectin, ICAM-1, VCAM-1, TNFalpha, IL1alpha, IL1beta, IL6 and IL8 expression. These results show that incision of the skin under aseptic conditions during elective standardized vascular surgery induces local nonspecific cellular inflammation.
 ...
PMID:Local cellular inflammation as a result of elective standardized vascular surgery. 1136 95

The chemokine IL-8 is found on the luminal side of vascular endothelial cells, where it is postulated to be immobilized during inflammation. In this study, we observed that immobilized IL-8 can stimulate neutrophils to firmly adhere to a substrate containing ICAM-1 in a static adhesion assay. Soluble IL-8 was then perfused over neutrophils rolling on P-selectin (P-sel) and ICAM-1, confirming that IL-8 in solution can quickly cause rolling neutrophils to arrest. To mimic a blood vessel wall with IL-8 expressed on the luminal surface of endothelial cells, IL-8 was immobilized along with P-sel and ICAM-1 at defined site densities to a surface. Neutrophils rolled an average of 200 microm on surfaces of P-sel, ICAM-1, and IL-8 before firmly adhering through ICAM-1-beta(2) integrin interactions at 2 dynes/cm(2) wall shear stress. Increasing the density of IL-8 from 60 to 350 sites/microm(2) on the surface decreased by 50% the average distance and time the neutrophils rolled before becoming firmly adherent. Temporal dynamics of ICAM-1-beta(2) integrin interactions of rolling neutrophils following IL-8 exposure suggest the existence of two classes of beta(2) integrin-ICAM-1 interactions, a low avidity interaction with a 65% increase in pause times as compared with P-sel-P-sel glycoprotein ligand-1 interactions, and a high avidity interaction with pause times 400% greater than the selectin interactions. Based on the proportionality between IL-8 site density and time to arrest, it appears that neutrophils may need to sample a critical number of IL-8 molecules presented by the vessel wall before forming a sufficient number of high avidity beta(2) integrin bonds for firm adhesion.
 ...
PMID:Immobilized IL-8 triggers progressive activation of neutrophils rolling in vitro on P-selectin and intercellular adhesion molecule-1. 1156 21

Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.
 ...
PMID:Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines. 1156 29

NF-kappaB/Rel transcription factors have been implicated in the differentiation of monocytes to either dendritic cells (DCs) or macrophages, as well as in the maturation of DCs from antigen-processing to antigen-presenting cells. Recent studies of the expression pattern of Rel proteins and their inhibitors (IkappaBs) suggest that their regulation during this differentiation process is transcriptional. To investigate differential gene expression between macrophages and DCs, we used commercially available gene microarrays (GEArray KIT), which included four of the NF-kappaB/Rel family genes (p50/p105, p52/p100, RelB, and c-rel) and 32 additional genes either in the NF-kappaB signal transduction pathway or under transcriptional control of NF-kappaB/Rel factors. To generate macrophages and DCs, human adherent peripheral blood monocytes were cultured with M-CSF or GM-CSF + IL-4 respectively for up to 8 days. DCs (and in some experiments, macrophages) were treated with lipopolysaccharide (LPS) for the last 48 h of culture to induce maturation. Cells were harvested after 7 days, cDNA was prepared and radiolabeled with alpha-(32)P-dCTP, then hybridized to gene arrays containing specific gene probes. beta-actin and GAPDH or PUC18 oligonucleotides served as positive or negative controls, respectively. The expression of all four NF-kappaB/Rel family genes examined was significantly upregulated in maturing DCs compared to macrophages. The strongest difference was observed for c-rel. RT-PCR determinations of c-rel, RelB, and p105 mRNAs confirmed these observations. Among the 32 NF-kappaB/Rel pathway genes, 14 were upregulated in mature DCs compared to macrophages. These genes were IkappaBalpha, IKK-beta, NIK, ICAM-1, P-selectin, E-selectin, TNF-alpha, TNFR2, TNFAIP3, IL-1alpha, IL-1R1, IL-1R2, IRAK, and TANK. By contrast, only mcp-1 (monocyte chemotactic protein 1) was upregulated in macrophages compared to DCs. NF-kappaB pathway genes upregulated in DCs compared to macrophages were constitutively expressed in monocytes then selectively downregulated during macrophage but not DC differentiation. LPS did not induce expression of most of these genes in macrophages but LPS did induce upregulation of IL-8 in mature macrophages. We conclude that NF-kappaB/Rel family genes, especially c-rel, are selectively expressed during differentiation of monocytes towards DCs. Moreover, this differential expression is associated both with activation of different NF-kappaB signal transduction pathways in DCs and macrophages and with expression of a unique subset of genes in DCs that are transcriptionally targeted by NF-kappaB/Rel factors. The results illustrate the ability of the NF-kappaB pathway to respond to differentiation stimuli by activating in a cell-specific manner unique signalling pathways and subsets of NF-kappaB target genes.
 ...
PMID:Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling. 1157 45

The effects of human platelets on interleukin (IL)-8 production from human peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) stimulated with the fungal (1-->3)-beta-D-glucan schizophyllan (SPG) were examined using ELISA. PBMCs/PMNs in the presence of platelets and SPG enhanced IL-8 production in comparison with those in the presence of either platelets or SPG. IL-8 production was dependent on the concentration of platelets and incubation time, and the activity reached the maximal level at 18 h of incubation. These activities were also observed with the addition of platelets prestimulated with SPG to PBMCs. Addition of SPG directly enhanced expression of P-selectin on platelet membrane surfaces. These results suggest that platelets play a key role in the cytokine production of leukocytes induced by fungal (1-->3)-beta-D-glucans and might be mediated, at least in part, by P-selectin.
 ...
PMID:Synergistic action of beta-glucan and platelets on interleukin-8 production by human peripheral blood leukocytes. 1182 47

The effects of WR1065 (SH), the free thiol form of amifostine, on nuclear transcription factor kappaB (NFkappaB) activation, manganese superoxide dismutase (MnSOD) gene expression, and secretion of human vascular endothelial cell growth factor (hVEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin, and interleukins IL-1alpha, IL-6, and IL-8 were investigated and compared in human microvascular endothelial (HMEC) and human glioma cells. WR1065 was evaluated at 2 concentrations, 4 mmol/L, ie, its most effective cytoprotective dose, and 40 micromol/L, a noncytoprotective but highly effective dose capable of preventing radiation and chemotherapeutic drug-induced mutations in exposed cells. A 30-minute exposure of HMEC and glioma cell lines U87 and U251 to WR1065 at either of the concentrations resulted in a marked activation of NFkappaB as determined by a gel shift assay, with the maximum effect observed between 30 minutes and 1 hour after treatment. Using a supershift assay, WR1065 exposure was observed to affect only the p50-p65 heterodimer, and not the homodimers or heterodimers containing p52 or c-Rel subunits of NFkappaB. WR1065 was also found to enhance MnSOD gene expression in both HMEC and glioma cells. Gene expression was enhanced 1.8-fold over control levels in HMEC over a period ranging from 12 to 24 hours after the time of maximum activation of NFkappaB. In contrast, MnSOD gene expression in U87 cells rose 3.5 times above control levels over this same period. WR1065 had no effect on the levels of adhesion molecules, cytokines, and growth factors secreted by cells exposed for up to 24 hours as measured by enzyme-linked immunosorbent assay.
 ...
PMID:Differential activation of nuclear transcription factor kappaB, gene expression, and proteins by amifostine's free thiol in human microvascular endothelial and glioma cells. 1191 94

Skin equivalents based on reconstituted human epidermis have been used recently to establish models for allergic/irritant contact dermatitis and cutaneous candidosis. In the present study the cytokine expression pattern and the morphological alterations in experimental cutaneous candidosis were investigated by RT-PCR and histological analysis. In experimental cutaneous C albicans infection the mRNA expression levels of interleukin (IL)-1a, IL-1beta, IL-8, GM-CSF, Exodus-2, tumour necrosis factor-alpha and PSL (P-selectin ligand) were upregulated. Cytokine profile and histological features of infected skin (separation of keratinocytes, oedema, vacuolisation) were comparable to that seen in experimental contact dermatitis. These immunomodulatory and morphological similarities might reflect a common pathogenesis factor in both diseases.
 ...
PMID:Cytokine expression induced by Candida albicans in a model of cutaneous candidosis based on reconstituted human epidermis. 1217 Dec 98


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