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)

Connective tissue activating peptide-III (CTAP-III) is a component of platelet alpha-granules which elicits a series of responses in connective tissue cells referred to as activation, including increased glucose consumption and mitogenesis and increased secretion of hyaluronic acid and glycosaminoglycans. As anticipated by a requirement for glucose or glucose precursors in the activation process, an early event following CTAP-III activation of connective tissue cells is an increase in glucose transport. The present study investigates the molecular basis for this increase in glucose transport. Murine 3T3-F442A fibroblasts were found to respond to CTAP-III in a manner similar to human connective tissue cells (synovial cells, chondrocytes, skin fibroblasts). CTAP-III increases the rate of glucose transport to similar extents at 4 and 24 h, and at physiologic (micrograms/ml) concentrations of CTAP-III. A proteolytic cleavage product of recombinant CTAP-III (rCTAP-III-Leu-21 (des-1-15)), also known as neutrophil-activating peptide-2 (NAP-2), was found to be equally effective as CTAP-III, whereas NAP-1/interleukin-8, another member of the CTAP-III super-family, was ineffective in stimulating glucose transport. This contrasts with neutrophil chemotaxis, in which CTAP-III (des-1-15)/NAP-2 acts similarly to NAP-1/interleukin 8 while CTAP-III is ineffective. CTAP-III appears to elicit a different type of glucose transport response than many other growth factors in that its response is sustained (greater than or equal to 24 h) rather than transient (peak approximately 4 h) in confluent as well as in subconfluent cells. Western blot analysis using antibodies to the GLUT-1 glucose transporter revealed an increased level of GLUT-1 protein in response to CTAP-III isoforms that corresponded in magnitude (on a percentage basis) to the increased level of glucose transport. The increased levels of GLUT-1 protein in response to CTAP-III and rCTAP-III-Leu-21 (des-1-15)/NAP-2 were accompanied by an increase in levels of GLUT-1 mRNA of a magnitude sufficient to account for observed increased levels of GLUT-1. These results are consistent with CTAP-III isoforms stimulating glucose transport in connective tissue cells by increasing levels of GLUT-1 mRNA and is one of the few known instances in which increases in levels of GLUT-1 mRNA and protein are sufficient to account for observed increases in glucose transport. They also provide further evidence that CTAP-III (des-1-15)/NAP-2 binds to more than one type of receptor and that CTAP-III acts in a manner different than other well characterized growth factors (e.g. platelet-derived growth factor, transforming growth factor-beta) in that it causes a sustained (greater than or equal to 24 h) elevation in glucose transport in confluent as well as subconfluent cells.
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PMID:Regulation of glucose transporters by connective tissue activating peptide-III isoforms. 152 75

We have tested the possible physical interactions between the iC3b receptor (CR3), lymphocyte function-associated Ag-1, and class III Fc gamma receptor (Fc gamma RIII) at neutrophil surfaces. Cells were labeled using fluorochrome-conjugated Fab or F(ab')2 fragments of antireceptor mAb. Labeled receptors were capped using second-step F(ab')2 fragments of goat anti-mouse Fab antiserum. After 20 min at 37 degrees C, 68% of the cells capped the anti-CR3 plus second-step complex. Capping was time, temperature, and cytochalasin B sensitive. When capped cells were probed with Fab' or F(ab')2 fragments of anti-Fc gamma RIII labeled with a distinct fluorochrome, 41% of the cells cocapped Fc gamma RIII. Indistinguishable results were obtained when potential antibody combining sites within caps were blocked with a large excess of Fab or F(ab')2 fragments. When Fc gamma RIII was capped, 49% of the cells cocapped CR3. Similarly, LFA-1 cocapped with both CR3 and Fc gamma RIII. Importantly, other membrane components including HLA class I, Mo5, CD13, CR type 1, and IL-8 receptors and N-4-nitrobenzo-2-oxa-1, 3-diszole L-alpha-dimyristoyl phosphatidylethanolamine did not cocap with CR3. However, the positive control Con A did cocap with CR3 and Fc gamma RIII. We next evaluated the effect of saccharides on CR3-Fc gamma RIII cocapping and found that 0.15 M N-acetyl-D-glucosamine (NADG), alpha-methyl-D-mannoside, and D-mannose significantly inhibited cocapping by 70, 58, and 48%, respectively. No inhibition was obtained using glucose, galactose, N-acetyl-neuraminic acid, fucose, sorbitol, fructose, or sucrose. Similarly, Fc gamma RIII-lymphocyte function-associated-1 cocapping was inhibited by NADG. However, the cocapping of CR3 with lymphocyte function-associated-1 or Con A were not affected by 0.15 M NADG, which suggests that NADG inhibition of leukoadhesin-Fc gamma RIII cocapping is not due to a general effect of NADG on capping. Inasmuch as Fc gamma RIII is a glycophospholipid-linked membrane protein, we speculate that it interacts with CR3 and/or lymphocyte function-associated-1 via lectin-like interactions.
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PMID:Cocapping of the leukoadhesin molecules complement receptor type 3 and lymphocyte function-associated antigen-1 with Fc gamma receptor III on human neutrophils. Possible role of lectin-like interactions. 768 Oct 86

IL-8 was measured in knee joint synovial fluid of 60 patients with rheumatoid arthritis, 8 with gout, 6 with osteoarthritis and 4 with meniscus lesions. IL-8 could be demonstrated in most SF samples. The highest levels were observed in rheumatoid joint effusions, yet mean levels were not significantly different between the different subgroups (mean +/- SE; RA 1537 +/- 3049 pg/ml, gout 570 +/- 952 pg/ml, OA/ML 178 +/- 188 pg/ml). In RA patients, IL-8 levels could not be related to various serological, clinical or radiological parameters. However, a correlation was observed between SF levels of IL-8 with those of lactate, LDH, beta 2-microglobulin and glucose. These observations suggest that next to the laboratory parameters IL-8 will be a parameter of the activity of the local inflammatory process. The results also demonstrate that IL-8 is not a disease-specific marker of joint inflammation.
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PMID:Interleukin-8 (IL-8) in synovial fluid of rheumatoid and nonrheumatoid joint effusions. 812 12

Per protocol, adults with an Injury Severity Score of 18 or greater underwent Candida antigen titer measurements weekly. If titers were 1:4 or greater, neutrophil function against Candida albicans was determined with use of a tritiated glucose incorporation assay, and polymorphonuclear leukocytes obtained from healthy blood donors were studied concurrently for comparison. Polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated titers were able to inhibit C albicans growth in a dose-dependent fashion. Polymorphonuclear leukocytes from injured patients with elevated titers had a significantly depressed ability to inhibit Calbicans growth compared with those from healthy blood donors at all effector cell-to-target cell ratios tested. Cytokine-treated polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated Candida antigen titers demonstrated significantly improved anticandidal activity at all ratios of polymorphonuclear leukocytes-to-Candida. Granulocyte macrophage-colony stimulating factor was the most potent cytokine at reconstituting polymorphonuclear leukocyte function, followed by interferon gamma and interleukin 8. In conclusion, an elevated Candida antigen titer in injured adults is associated with impaired polymorphonuclear leukocyte antifungal activity. This depressed activity can be reconstituted by the addition of cytokine.
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PMID:Impaired polymorphonuclear leukocyte anticandidal function in injured adults with elevated Candida antigen titers. 841 79

Within the limitations of the various experimental protocols there appears to be agreement in the literature that unused dialysis fluids, at least when studied in vitro, adversely affect multiple leukocyte functions. The effects of dialysis fluids on leukocytes that have been reported to date include: 1. Decreased cell viability of PMNs, PM phis, PBMCs, and lymphocytes; 2. Inhibited phagocytosis and bacterial killing of various microorganisms by PM phis, PMNs, and peripheral blood leukocytes; 3. Reduced secretion of leukotrienes (LTB4, LTC4) from peritoneal and peripheral blood PMNs and PBMCs; 4. Reduced secretion of prostaglandins (PGE2, TXB2 and 6-keto-PGF1 alpha) from PM phi; 5. Decreased production of many cytokines including TNF alpha, IL-8, and IL-6 in PM phis and PBMCs. In addition, several studies targeting the potential mechanisms by which dialysis solutions inhibit leukocyte function identified the initial low pH of the fluids in combination with their lactate content as being of primary relevance, since they may lead to a rapid intracellular acidification of leukocytes. Moreover, some studies indicated the importance of fluid hyperosmolarity and excessive glucose concentrations. These results are indirectly supported by recent in vitro investigations of alternative fluids, which showed improved leukocyte function following exposure to solutions with neutral pH, bicarbonate buffer instead of lactate, or normal osmolarity due to use of an alternative osmotic agent (e.g., glucose polymer). In conclusion, the evidence obtained during in vitro experimentation suggests that current dialysis fluids are, indeed, not biocompatible. However, whether this also bears physiological relevance in vivo remains to be established in controlled clinical trials comparing conventional fluids to alternative solutions with improved biocompatibility. With regard to the future development of in vitro models for biocompatibility assessment, the following guidelines are suggested: 1. Cell functional parameters should be studied in more than one cell population; 2. Depending on which fluid aspect is under investigation, short or even very short exposure times should be used (e.g., < 30 min for pH/buffer studies; < 4 hours for osmolality/osmotic agent studies); 3. In case the parameter/readout of interest requires longer study periods than indicated above (e.g., studies of cytokine induction or surface receptor expression), preincubation/recovery models should be preferred over coincubation experiments.
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PMID:In vitro studies on the effect of dialysis solutions on peritoneal leukocytes. 855 25

The antiinflammatory mediators interleukin (IL)-10 and soluble tumor necrosis factor (TNF) receptors p55 (sTNFR-55) and sTNFR-75 in cerebrospinal fluid (CSF) from 37 children with bacterial meningitis were studied. CSF concentrations of IL-10, sTNFR-55, and sTNFR-75 and of the proinflammatory cytokines TNF-alpha, IL-6, and IL-8 were markedly elevated and were, with the exception of the sTNFRs, significantly higher in CSF than in serum. CSF concentrations of sTNFR- 55 and sTNFR-75 were only associated positively with IL-10 levels. CSF glucose levels correlated highly with levels of IL-10, sTNFR-55, and sTNFR-75 and weakly with TNF-alpha and IL-6. Cytokine levels in CSF decreased rapidly, while sTNFR levels remained elevated for at least 24 h.
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PMID:Interleukin-10 and soluble tumor necrosis factor receptors in cerebrospinal fluid of children with bacterial meningitis. 864 29

Cytokines are released from activated cells during acute and chronic pathologic processes including infection and malignancy. These processes and immunotherapy with cytokines are frequently accompanied by feeding suppression. The intracerebroventricular (ICV) microinfusion of low doses of interleukin 1 beta (IL-1 beta) decreases short- and long-term food intake by reducing meal size and meal duration; high amounts also decrease meal frequency and prolong intermeal intervals. The ICV microinfusion of interferon (IFN) suppresses only short-term feeding by reducing meal size and meal duration; IL-8 suppresses short-term feeding by reducing meal size. Bacterial lipopolysaccharide also reduces meal size. IL-1 beta is significantly more potent than IFN, IL-8, and other cytokines. Evidence also shows that only a subset of cytokines released during pathologic processes participate in the regulation of feeding. These behavioral effects of cytokines are blocked by the appropriate receptor antagonists and monoclonal antibodies. Cytokines affect the hypothalamus and this may result in feeding suppression. IL-1 beta and IFN act directly and specifically on the glucose-sensitive neurons in the ventromedial hypothalamic nucleus (a "satiety" site) and the lateral hypothalamic area (a "hunger" site). Pathophysiologic concentrations of IL-1 beta and IL-2 in the cerebrospinal fluid inhibit the calcium channel current in neurons. It is essential to characterize the mechanisms by which cytokines induce feeding suppression to understand appetite suppression during disease and immunotherapy.
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PMID:Cytokines and feeding suppression: an integrative view from neurologic to molecular levels. 874 49

Ischemia is an interruption of oxygen and nutrient supply to a determined area of tissue for a period of time. Because of the heterogeneity of various tissues with regard to their microvascular flow reserve and oxidative capacity, as well as their markedly different metabolic needs, a single critical Po2 level below which ischemia occurs is unlikely. This is why there are variations of tolerance to hypoxia within and among organs. In general, when Pao2 reaches approximately 5 torr there is already evidence, in some organs, of altered cellular energetics. In addition, cessation of flow impairs the incoming transfer of nutrients such as glucose, and cells must depend on their own intracellular stores of carbon radicals, if available. Epidemiologic data suggest that there are deleterious effects of hypoxia on the immune system and that these effects result in increased susceptibility to infection. The histology of ischemic tissues demonstrates intravascular neutrophil (PMN) accumulation, vascular damage, and increased vascular permeability. Expression of PMN adhesion receptors is increased when oxygen is nearly completely removed from the medium. Expression of integrins on the cell surface is regulated by intracellular calcium; hypoxia causes a sustained and prolonged increase of intracellular calcium levels. Because both granule movement and functional expression of adhesion receptors on the cell surface are important in leukocyte motility, chemotaxis, and phagocytosis, these functions may be impaired by hypoxia. Exposure of a human macrophage cell line to nonlethal levels of hypoxia causes in vitro release of significant amounts of biologically active cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1 and IL-8, as well as expression of intercellular adhesion molecule-1 and bound and soluble receptors for TNF alpha. Hypoxia markedly decreases T-lymphocyte IL-2 messenger RNA, a key cytokine responsible for B-cell proliferation and immunoglobulin secretion.
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PMID:Leukocyte responses to hypoxic/ischemic conditions. 877 94

Chronic hyperglycemia is thought to be important in the development of diabetic neovascularization but the mechanisms involved remain poorly understood. Interleukin-8 (IL-8) is a leukocyte chemokine and activating agent with angiogenic properties that is present in diabetic vitreous and may play a role in diabetic vasculopathy. We studied IL-8 and monocyte chemotactic protein-1 (MCP-1) production by human retinal pigment epithelial (hRPE) cells exposed to glycated human serum albumin (GHSA). Enzyme-linked immunoassay GHSA (500 micrograms/mL)-treated hRPE cells secreted levels of IL-8 and MCP-1 detectable within 4 h and reached 26.0 +/- 1.3 and 42.2 0.4 ng/10(6) cells/mL after 24 h, respectively. Induction of IL-8 and MCP-1 by GHSA at concentrations ranging from 62.5 to 3,000 micrograms/mL exhibited dose-dependent kinetics. The GHSA-induced chemokine secretion by hRPE was almost completely inhibited by actinomycin D and cycloheximide, suggesting that de novo mRNA and protein synthesis are necessary for the GHSA-induced IL-8 and MCP-1 production. Northern blot analysis of GHSA-induced hRPE IL-8 and MCP-1 mRNA expression corresponded to the time- and dose-dependent increases measured by enzyme-linked immunosorbent assay. High concentrations of glucose (20 mM; 360 mg/dl) increased GHSA-induced hRPE IL-8 and MCP-1 secretion, whereas added insulin (0.5 ng/mL) inhibited IL-8 but not MCP-1 protein secretion and mRNA expression. GHSA also induced hRPE to secrete GRO-alpha, RANTES, and NAP-2 chemokines. GHSA induction of hRPE chemokines further suggests a role for the hRPE in leukocyte infiltration, vascular injury, and neovascularization.
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PMID:Glycated serum albumin induces chemokine gene expression in human retinal pigment epithelial cells. 883 Jul 98

The biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid (AA-PDF) was compared to that of a 2.27% glucose-based peritoneal dialysis fluid (G-PDF). Peritoneal macrophages (PMO), isolated from the peritoneal dialysis (PD) effluents of 10 chronic ambulatory PD patients, were tested for their phagocytosis capacity and peak chemiluminescence response. A subset of PMO was cultured for 24 h with and without lipopolysaccharide (LPS) to study the release of interleukin-1 beta (IL-1 beta) and 8 (IL-8). As control, the interleukin release by blood monocytes of healthy donors was tested. The opsonic activity of the PD effluent was tested as well. Compared to PMO isolated from G-PDF, PMO from AA-PDF showed a significantly better phagocytosis capacity. There was no difference in the peak chemiluminescence response between PMO from AA-PDF and G-PDF. The release of IL-1 beta by unstimulated PMO isolated from the two fluids did not differ. Compared to control monocytes, however, PMO from both fluids showed a considerable spontaneous release of IL-1 beta. When stimulated with LPS, IL-1 beta production by PMO from G-PDF exceeded that of PMO from AA-PDF (p < 0.002). The release of IL-8 by PMO from G-PDF was significantly higher in comparison with PMO from AA-PDF, both spontaneously and after stimulation with LPS (p < 0.02). The opsonic activity of undiluted and to 75% diluted effluents was significantly higher for G-PDF than for AA-PDF (p < 0.01). Thus, compared to the regularly used G-PDF, the phagocytosis capacity as measure for PMO function seems to be better preserved after in vivo exposure to AA-PDF. In addition, the higher release of IL-1 beta and IL-8 by PMO isolated from G-PDF suggests a stronger intra-abdominal activation of PMO, with G-PDF acting as a chemical inflammatory agent. Whether the lower opsonic activity of the AA-PDF is more important for biocompatibility than the other parameters is not clear. Therefore, it is concluded that, although macrophage function is better preserved, it is not proven that the 1.1% AA-PDF studied has an improved biocompatibility compared to 2.27% G-PDF.
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PMID:Biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid compared to a 2.27% glucose-based peritoneal dialysis fluid. 888 16


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