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)

Perinatal hypoxic-ischaemic brain damage is an important cause of neonatal death and permanent neurological impairment. Therapeutic hypothermia may reduce the development of brain damage after hypoxia. Whether to use room-air or 100% oxygen for resuscitation of the asphyxiated neonate is still debated, and there is little knowledge about the combined effects of therapeutic hypothermia and room air resuscitation. We used human NT2-N neurons to test whether oxygen level during reoxygenation would influence the protective effect of hypothermia. Oxygen-glucose deprived (OGD) human NT2-N neurons were exposed to 20 min of low (1%), medium (21%) or high (95%) oxygen concentrations immediately after hypoxia, followed by 20.5 h of hypothermia (33 degrees C) or normothermia (37 degrees C). Cell viability was determined by a methyltetrazolium assay (MTT), cellular energy failure by hypoxanthine release to supernatant, and inflammatory response by the release of IL-8 (Interleukin-8), bFGF (basic fibroblast growth factor), IP-10 (interferon-inducible protein-10) and MCP-1 (monocyte chemotactic protein-1) to supernatant. Post-hypoxic hypothermia resulted in significantly higher MTT cleavage (average 27% of control (SD 11%) vs 24% (SD 12%), p=0.005). Hypoxanthine release was increased both immediately after hypoxia and 21 h later, however less in hypothermic (median increase 2.0 mumol/L, IQR 1.2-3.2) compared to normothermic cells (2.7 mumol/L, IQR 2.1-4.1, p<0.05). All four inflammatory markers increased after hypoxia but not differently between normothermic and hypothermic cells. Oxygen level had no significant effect on cell viability, inflammatory markers or energy status, irrespective of temperature level. We conclude that hypothermia protects isolated neurons after in vitro hypoxia, and that this protection is not affected by hyperoxic, normoxic or hypoxic reoxygenation.
 ...
PMID:Post-hypoxic hypothermia is protective in human NT2-N neurons regardless of oxygen concentration during reoxygenation. 1914 35

The aim of this study was to compare the acute effect of (i) meals rich in saturated fat, oleic acid, and alpha-linolenic acid and (ii) meals rich in starch and fiber on markers of inflammation and oxidative stress in obese and lean women. In a crossover study, 15 abdominally obese women (age, 54 +/- 9 years; BMI, 37.3 +/- 5.5 kg/m2) and 14 lean women (age, 53 +/- 10 years; BMI, 22.9 +/- 1.9 kg/m2) consumed meals rich in cream (CR), olive oil (OL), canola oil (CAN), potato (POT), and All-Bran (BRAN) in random order. Blood samples were collected before and up to 6 h after the meals and plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), lipid peroxides (LPOs), free-fatty acids (FFAs), insulin, glucose, and cortisol were measured. Plasma IL-6 decreased significantly 1 h after the meals then increased significantly above baseline at 4h and 6h in obese women and at 6h in lean women. The incremental area under the curve (iAUC) for IL-6 was significantly (P = 0.02) higher in obese compared with lean women and was significantly lower following the high fiber BRAN meal compared with a POT meal (P = 0.003). Waist circumference (R = 0.491, P = 0.007) and cortisol AUC (R = -0.415, P = 0.03) were significant determinants of the magnitude of 6h changes in plasma IL-6 after the meals. These findings suggest that the postprandial response of plasma IL-6 concentrations may be influenced by the type of carbohydrate in the meal, central adiposity, and circulating cortisol concentrations in women.
 ...
PMID:Postprandial cytokine concentrations and meal composition in obese and lean women. 1918 29

Hyperglycemic crises of diabetic ketoacidosis and nonketotic hyperglycemia are associated with elevation of counterregulatory hormones and proinflammatory cytokines, markers of lipid peroxidation, and oxidative stress. To investigate if other conditions besides hyperglycemia could evoke such a prompt increase in cytokine levels, lipid peroxidation, and oxidative stress markers, we induced hypoglycemic stress by standard insulin tolerance test and measured proinflammatory cytokines, markers of lipid peroxidation, reactive oxygen species (ROS), and counterregulatory hormones. Insulin tolerance test was performed in 13 healthy male subjects with no history of infection, cardiovascular risk factors, or abnormal glucose. At baseline and at 30, 45, 60, 120, and 240 minutes after insulin injection, the following parameters were measured: glucose, cortisol, corticotropin, epinephrine (EP), norepinephrine (NE), growth hormone, tumor necrosis factor (TNF)-alpha, interleukin (IL) 1beta, IL-6, IL-8, free fatty acids, white blood cells, lipid peroxidation markers by thiobarbituric acid assay, and ROS by dichlorofluorescein method. The peak value of white blood cell count at 120 minutes was significantly associated with the peak values of NE at 30 minutes and cortisol at 60 minutes. By comparing the area under the curve of measured parameters, EP emerged as significant predictor of TNF-alpha (P = .05) and IL-8 (P = .027). Cortisol emerged as predictor of IL-1beta significantly (P = .05). Corticotropin predicted area under the curve of IL-6 with borderline significance (P = .06). In the present study, insulin-induced hypoglycemia in nondiabetic male subjects is associated with increased proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6, and IL-8), markers of lipid peroxidation, ROS, and leukocytosis. Elevations of NE, EP, corticotropin, and cortisol in hypoglycaemia are associated with the elevation of the proinflammatory cytokines and leukocytosis.
 ...
PMID:Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. 1930 62

We evaluated the healing potential of human fetal aorta-derived CD133(+) progenitor cells and their conditioned medium (CD133(+) CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2x10(4) CD133(+) or CD133(-) cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133(+) cells expressed high levels of wingless (Wnt) genes, which were downregulated following differentiation into CD133(-) cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133(+) cells accelerated wound closure as compared with CD133(-) or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133(+) cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133(+) CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by co-administering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133(+) CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of Wnt expression. The promigratory and proangiogenic effect of CD133(+) CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. CD133(+) cells stimulate wound healing by paracrine mechanisms that activate Wnt signaling pathway in recipients. These preclinical findings open new perspectives for the cure of diabetic ulcers.
 ...
PMID:Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling. 1960 84

The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds found in mangosteen and are reported to have antiinflammatory properties in several murine models. Given the association between obesity, chronic low-grade inflammation, and insulin resistance, we examined the effects of alpha- and gamma-MG on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with lipopolysaccharide (LPS). alpha- and gamma-MG decreased the induction by LPS of inflammatory genes, including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant protein-1, and Toll-like receptor-2. Moreover, alpha- and gamma-MG attenuated LPS activation of the mitogen-activated protein kinases (MAPK) c-jun NH(2)-terminal kinase, extracellular signal-related kinase, and p38. alpha- and gamma-MG also attenuated LPS activation of c-Jun and activator protein (AP)-1 activity. gamma-MG was more effective than alpha-MG on an equimolar basis. Furthermore, gamma-MG but not alpha-MG attenuated LPS-mediated IkappaB-alpha degradation and nuclear factor-kappaB (NF-kappaB) activity. In addition, gamma-MG prevented the suppression by LPS of insulin-stimulated glucose uptake and PPAR-gamma and adiponectin gene expression. Taken together, these data demonstrate that MG attenuates LPS-mediated inflammation and insulin resistance in human adipocytes, possibly by inhibiting the activation of MAPK, NF-kappaB, and AP-1.
 ...
PMID:Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and insulin resistance in primary cultures of human adipocytes. 1940 22

Innate mucosal immune responses, including recognition of pathogen-associated molecular patterns through Toll-like receptors, play an important role in preventing infection in the female reproductive tract (FRT). Damaged cells release nucleotides, including ATP and uridine 5'-diphosphoglucose (UDP-glucose), during inflammation and mechanical stress. We show in this report that P2RY14, a membrane receptor for UDP-glucose, is exclusively expressed in the epithelium, but not the stroma, of the FRT in humans and mice. P2RY14 and several proinflammatory cytokines, such as IL-8, are up-regulated in the endometria of patients with pelvic inflammatory disease. UDP-glucose stimulated IL-8 production via P2RY14 in human endometrial epithelial cells but not stromal cells. Furthermore, UDP-glucose enhanced neutrophil chemotaxis in the presence of a human endometrial epithelial cell line in an IL-8-dependent manner. Administration of UDP-glucose into the mouse uterus induced expression of macrophage inflammatory protein-2 and keratinocyte-derived cytokine, two murine chemokines that are functional homologues of IL-8, and augmented endometrial neutrophil recruitment. Reduced expression of P2RY14 by small interfering RNA gene silencing attenuated LPS- or UDP-glucose-induced leukocytosis in the mouse uterus. These results suggest that UDP-glucose and its receptor P2RY14 are key front line players able to trigger innate mucosal immune responses in the FRT bypassing the recognition of pathogen-associated molecular patterns. Our findings would significantly impact the strategic design of therapies to modulate mucosal immunity by targeting P2RY14.
 ...
PMID:The UDP-glucose receptor P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8. 1945 5

Intensive insulin therapy, aiming for strict normoglycaemia, is associated with increased survival in critically ill patients. Insulin therapy concomitantly reduces plasma-free fatty acids. Recent studies indicate that free fatty acids mediate inflammation. In addition to plasma glucose and free fatty acid-lowering effects, insulin also has anti-inflammatory properties. This study was designed to study the pro-inflammatory effects of two free fatty acid concentrations during acute endotoxaemia and controlled comparable levels of plasma glucose and insulin. Twenty pigs were anaesthetized and mechanically ventilated. Pigs were randomized to two different, constant Intralipid infusion rates, throughout observation. All pigs were administered continuous intravenous infusion of endotoxin and subjected to controlled levels of p-glucose (4.5 mmol/l) and insulin by use of a hyperinsulinaemic euglycaemic clamp. Changes in circulating tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, leucocytes, insulin, glucose, free fatty acids, triglycerides, albumin, blood gases, temperature, and, haemodynamic function were monitored. Immediately following killing, biopsies were taken from heart and kidney. Biopsies were analysed for protein content of TNF-alpha, IL-6, IL-8 and IL-10. Sustained elevated and significantly different plasma levels of free fatty acids were demonstrated between groups (mean free fatty acid concentrations, 1.62 mM versus 0.58 mM, p < 0.0002). Endotoxaemia induced a steep increase in plasma TNF-alpha, IL-6 and leucocytes, however, without differences between the low- and high-free fatty acid groups. Cytokine content in heart and kidney tissue was not modified by free fatty acids. Compared with the response obtained at lower free fatty acid levels, high free fatty acid levels did not exacerbate the inflammatory response to acute endotoxaemia. Our results do not support the role of free fatty acids as a significant pro-inflammatory mediator.
 ...
PMID:Circulating free fatty acids do not contribute to the acute systemic inflammatory response. an experimental study in porcine endotoxaemia. 1962 79

Microdialysis enables measurement of the chemistry of the cerebral extracellular fluid. This study's objective was to utilise microdialysis to monitor levels of glucose, lactate, pyruvate, glutamate and glycerol in patients following surgery for intrinsic brain tumours, and to assess the concentration of growth factors, cytokines and other proteins involved in the pathogenesis of high-grade gliomas in vivo. Eight patients with suspected high-grade gliomas were studied. Seven of these underwent resection with one microdialysis catheter placed at the tumour resection margin and, in six of these seven cases, a second microdialysis catheter in macroscopically normal peritumour tissue. The remaining glioma patient had an image-guided biopsy with a single catheter inserted stereotactically at the tumour margin. Histology demonstrated WHO IV glioblastoma in five cases, WHO III anaplastic astrocytoma in two cases, and one cerebral lymphoma. In the high-grade gliomas (WHO IV and III), tumour margin microdialysates consistently showed significantly lower glucose, higher lactate/pyruvate (L/P) ratio, higher glutamate and higher glycerol, relative to peritumour microdialysates (P < 0.05). These results indicate that malignant glioma margin tissue is metabolically extremely active. There was great variability in the microdialysate concentrations of growth factors (TGFalpha, EGF, VEGF), cytokines (IL-1alpha, IL-1beta, IL-1ra, IL-6, IL-8), matrix metalloproteinases (MMP-2, MMP-9) and their endogenous inhibitors (TIMP-1, TIMP-2). Notably, microdialysates from the glioma resection margin demonstrated significantly higher IL-8 concentration and higher MMP-2/TIMP-1 ratio when compared to peritumour microdialysates (P < 0.05), suggesting an environment favouring invasion and angiogenesis at the tumour margin. Microdialysis is a promising technique to study in vivo glioma metabolism, and may assist in the development of new therapies.
 ...
PMID:In vivo assessment of high-grade glioma biochemistry using microdialysis: a study of energy-related molecules, growth factors and cytokines. 1971 45

Adjunctive treatment to improve outcome from bacterial meningitis has centered on dexamethasone. Among Vietnamese patients with bacterial meningitis, cerebrospinal fluid (CSF) opening pressure and CSF:plasma glucose ratios were significantly improved and levels of CSF cytokines interleukin (IL)-6, IL-8, and IL-10 and were all statistically significantly lower after treatment in patients who were randomized to dexamethasone, compared with levels in patients who received placebo.
 ...
PMID:Immunological and biochemical correlates of adjunctive dexamethasone in Vietnamese adults with bacterial meningitis. 1981 25

Islets of patients with type 2 diabetes mellitus (T2DM) display features of an inflammatory process including elevated levels of the cytokine IL-1beta, various chemokines, and macrophages. IL-1beta is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation. Given the association of dyslipidemia and T2DM, we tested whether free fatty acids (FFA) promote the expression of proinflammatory factors in human and mouse islets and investigated a role for the IL-1RI in this response. A comparison of 22 mouse tissues revealed the highest IL-1RI expression levels in islets and MIN6 beta-cells. FFA induced IL-1beta, IL-6, and IL-8 in human islets and IL-1beta and KC in mouse islets. Elevated glucose concentrations enhanced FFA-induced proinflammatory factors in human islets. Blocking the IL-1RI with the IL-1R antagonist (IL-1Ra) strongly inhibited FFA-mediated expression of proinflammatory factors in human and mouse islets. Antibody inhibition of IL-1beta revealed that FFA stimulated IL-1RI activity via the induction of the receptor ligand. FFA-induced IL-1beta and KC expression in mouse islets was completely dependent on the IL-1R/Toll-like receptor (TLR) docking protein Myd88 and partly dependent on TLR2 and -4. Activation of TLR2 in purified human beta-cells and islets stimulated the expression of proinflammatory factors, and IL-1RI activity increased the TLR2 response in human islets. We conclude that FFA and TLR stimulation induce proinflammatory factors in islets and that IL-1RI engagement results in signal amplification.
 ...
PMID:Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I. 1981 43


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