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)

We examined the effect of high glucose concentrations on the production of interleukin(IL)-8, which seems to be important for the development of atherosclerosis, in cultured human aortic endothelial cells (AoEC) and smooth muscle cells (AoSMC). After incubating these cells with various concentrations of glucose for 2 days or 7 days, the IL-8 concentration in cell lysates was measured by enzyme-linked immunosorbent assay and the IL-8 mRNA expression was examined by Northern analysis. After 2 days' culture, 42.5 mmol/l glucose enhanced IL-8 mRNA expression in AoEC, but not in AoSMC, compared to 4 mmol/l glucose. After 7 days' culture, the IL-8 concentration in AoEC lysate and the expression of IL-8 mRNA were significantly increased by 20.5 mmol/l glucose, or 42.5 mmol/l glucose compared to 4 mmol/l glucose. On the other hand, the IL-8 concentration in AoSMC lysate was not affected by any glucose concentration and the expression of IL-8 mRNA in AoSMC was diminished by high glucose. These results suggest that the chemotactic gradient by IL-8 is established between arterial intima and media in response to high glucose levels in diabetic patients, and that it may be one of the key factors for SMC migration to the intima leading to diabetic macroangiopathy.
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PMID:High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy. 916 32

Plasma levels of interleukin 12 (IL-12), a cytokine consisting of two different polypeptide subunits (p40 and p35), were measured together with interferon gamma (IFN-gamma) and other cytokines in 46 children with septic shock and purpura. The median (range) plasma IL-12 p40 level on admission was 457 (244-2677) pg/ml in non-survivors vs 189 (< 40-521) pg/ml in survivors (P = < 0.001). IL-12 p70 levels were elevated in only nine patients. IL-12 p40 plasma levels were positively correlated with tumour necrosis factor alpha (TNF-alpha), IL-6, IL-8, IL-10 and PRISM-score, whereas they were negatively correlated with C-reactive protein (CRP), whole blood cell (WBC) and serum glucose levels. Twelve (29%) of the patients had detectable levels of IFN-gamma. Thus, circulating levels of IL-12 p40 and to a lesser extent those of IL-12 p70, are elevated in children with septic shock and purpura, and correlate with severity of disease and outcome.
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PMID:Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease. 932 21

5-Oxo-eicosatetraenoic acid (5-oxoETE) stimulated human neutrophil (PMN) and eosinophil chemotaxis, PMN hexose uptake, and PMN membrane GTP/GDP exchange. Pertussis toxin (PT), a blocker of heterotrimeric G proteins (GP), completely inhibited these responses, but proved far less effective on the same responses when elicited by leukotriene B4, C5a, FMLP, platelet-activating factor, IL-8, or RANTES chemotactic factors. 5-OxoETE also specifically bound to the membrane preparations that conducted GTP/GDP exchange. This binding was down-regulated by GTPgammaS, but not ADPgammaS, and displaced by 5-oxoETE analogues, but not by leukotriene B4, lipoxin A4, or lipoxin B4. Finally, PMN expressed PT-sensitive GP alphaiota2 and PT-resistant GP alphaq/11- and alpha13-chains; eosinophils expressed only alphai2 and alphaq/11. We conclude that 5-oxoETE activates granulocytes through a unique receptor that couples preferentially to PT-sensitive GP. The strict dependency of this putative receptor on PT-sensitive GP may underlie the limited actions of 5-oxoETE, compared with other CF, and help clarify the complex relations between receptors, GP, cell signals, and cell responses.
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PMID:The coupling of 5-oxo-eicosanoid receptors to heterotrimeric G proteins. 1070 29

The aim of this study was to assess the acute effects of cigarette smoke exposure on cellular and cytokine profile in BAL fluids in an isolated perfused rabbit assay. The experimental animals were categorized into four groups: (1) unexposed controls and (2) cigarette smoke-exposed animals perfused with autologous whole blood; (3) unexposed controls and cigarette smoke-exposed; (4) cigarette smoke-exposed animals perfused with Krebs' Ringer solution containing 5% bovine serum albumin and glucose. Cigarette smoke induced an increase in total cell numbers (mainly alveolar macrophages in BAL fluids) and an increase in the permeability index of BAL. Levels of interleukin 8 were also significantly decreased in BAL fluids due to acute effects of cigarette smoke exposure. The most likely explanation for cigarette smoke-induced increase of inflammatory cells in BAL in lungs is because of the release of pre-existing cells from reservoirs within the lungs. The acute effects of cigarette smoke-induced increase of pulmonary epithelial permeability may also play an important role in the cellular recruitment into airspaces from the lung reservoirs.
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PMID:Acute effects of smoke exposure on the cellular and cytokine profile in isolated perfused lungs. 1099 95

Peroxisome proliferator-activated (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. PPARs function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPARalpha is highly expressed in tissues such as liver, muscle, kidney and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPARgamma is predominantly expressed in intestine and adipose tissue. PPARgamma triggers adipocyte differentiation and promotes lipid storage. The hypolipidemic fibrates and the antidiabetic glitazones are synthetic ligands for PPARalpha and PPARgamma, respectively. Furthermore, fatty acids and eicosanoids are natural PPAR ligands: PPARalpha is activated by leukotriene B4, whereas prostaglandin J2 is a PPARgamma ligand. These observations suggested a potential role for PPARs not only in metabolic but also in inflammation control. The first evidence for a role of PPARalpha in inflammation control came from the demonstration that PPARalpha deficient mice display a prolonged response to inflammatory stimuli. It was suggested that PPARalpha deficiency results in a reduced beta-oxidative degradation of these inflammatory fatty acid derivatives. More recently, PPAR activators were shown to inhibit the activation of inflammatory response genes (such as IL-2, IL-6, IL-8, TNFalpha and metalloproteases) by negatively interfering with the NF- kappaB, STAT and AP-1 signalling pathways. PPAR activators exert these anti-inflammatory activities in different immunological and vascular wall cell types such as monocyte/macrophages, endothelial, epithelial and smooth muscle cells in which PPARs are expressed. These recent findings indicate a modulatory role for PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases, such as atherosclerosis and inflammatory bowel disease.
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PMID:Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. 1108

Strenuous exercise induces increased levels in a number of pro-and anti-inflammatory cytokines, natural occurring cytokine inhibitors, and chemokines. Thus, increased plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases as much as 100-fold after a marathon race. It has recently been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial concentration. Larger amounts of IL-6 are produced in response to exercise than any other cytokine, IL-6 is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose output and to induce lipolysis. These facts indicate that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.
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PMID:Exercise and interleukin-6. 1130 45

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPAR alpha is highly expressed in liver, muscle, kidney and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPAR gamma is predominantly expressed in intestine and adipose tissue, where it triggers adipocyte differentiation and promotes lipid storage. Recently, the expression of PPAR alpha and PPAR gamma was also reported in cells of the vascular wall, such as monocyte/macrophages, endothelial and smooth muscle cells. The hypolipidemic fibrates and the antidiabetic glitazones are synthetic ligands for PPAR alpha and PPAR gamma, respectively. Furthermore, fatty acid-derivatives and eicosanoids are natural PPAR ligands: PPAR alpha is activated by leukotriene B4, whereas prostaglandin J2 is a PPAR gamma ligand, as well as some components of oxidized LDL, such as 9- and 13-HODE. These observations suggested a potential role for PPARs not only in metabolic but also in inflammation control and, by consequence, in related diseases such as atherosclerosis. More recently, PPAR activators were shown to inhibit the activation of inflammatory response genes (such as IL-2, IL-6, IL-8, TNF alpha and metalloproteases) by negatively interfering with the NF-kappa B, STAT and AP-1 signalling pathways in cells of the vascular wall. Furthermore, PPARs may also control lipid metabolism in the cells of the atherosclerotic plaque. In addition, different clinical trials (such as the LOCAT, BECAIT and VA-HIT) as well as animal studies indicate that PPAR activators may have anti-atherogenic properties by reducing the progression of atherosclerotic lesions. In this review, we summarize the evidence indicating that PPAR alpha and PPAR gamma directly modulate vessel wall functions, and its consequences in the control of cardiovascular disease.
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PMID:Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall. 1137 25

The influence of carbohydrate (1 l/h of a 6% carbohydrate beverage), gender, and age on pro- and anti-inflammatory plasma cytokine and hormone changes was studied in 98 runners for 1.5 h after two competitive marathon races. The marathoner runners were randomly assigned to carbohydrate (C, n = 48) and placebo (P, n = 50) groups, with beverages administered during the races in a double-blind fashion using color codes. Plasma glucose was higher and cortisol was lower in the C than in the P group after the race (P < 0.001). For all subjects combined, plasma levels of interleukin (IL)-10, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 rose significantly immediately after the race and remained above prerace levels 1.5 h later. The pattern of change in all cytokines did not differ significantly between the 12 women and 86 men in the study and the 23 subjects > or =50 yr of age and the 75 subjects <50 yr of age. The pattern of change in IL-10, IL-1ra, and IL-8, but not IL-6, differed significantly between the C and the P group, with higher postrace values measured for IL-10 (109% higher) and IL-1ra (212%) in the P group and for IL-8 (42%) in the C group. In conclusion, plasma levels of IL-10, IL-1ra, IL-6, and IL-8 rose strongly in runners after a competitive marathon, and this was not influenced by age or gender. Carbohydrate ingestion, however, had a major effect in attenuating increases in cortisol and two anti-inflammatory cytokines, IL-10 and IL-1ra.
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PMID:Cytokine changes after a marathon race. 1140 20

The peroxisome proliferator-activated receptors (PPARs) are nuclear hormone transcription factors that regulate genes associated with lipid and glucose metabolism. Recent evidence suggests that PPAR-gamma may also act as a negative immunomodulator. To investigate the potential role of PPAR-gamma in regulating airway inflammation, we characterized the expression and function of PPAR-gamma in airway epithelial cells. Airway epithelial cells constitutively express PPAR-gamma-specific messenger RNA and protein. Further, airway epithelial PPAR-gamma is inducible by interleukin (IL)-4 in NIH-A549 cells. Two PPAR-gamma agonists, the prostaglandin D2 metabolite 15-deoxy-(Delta)(12,14) prostaglandin J2 (15d-PGJ2) and a thiazolidinedione, ciglitazone, were used to study the effects of PPAR-gamma activation on airway epithelial cytokine expression. Activation of PPAR-gamma stimulated a PPAR-responsive reporter gene in a ligand-specific manner. In NIH-A549 cells, both ligands also blocked the cytokine-induced expression of the inducible form of nitric oxide synthase in a dose-dependent manner. In contrast, ciglitazone alone had a slight effect on cytokine-induced IL-8 secretion, but markedly inhibited IL-8 secretion from cells pretreated with IL-4. The demonstration of PPAR-gamma expression and function in airway epithelial cells expands the immunoregulatory role of PPARs and suggests a critical role for PPAR-gamma in antagonizing proinflammatory pathways in the airways.
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PMID:Peroxisome proliferator-activated receptor-gamma regulates airway epithelial cell activation. 1141 33

Brain inflammation has been implicated in the development of brain edema and secondary brain damage in ischemia and trauma. Mechanisms involved in leukocyte infiltration across the blood-brain barrier are still unknown. In this study, we show that human cere-bromicrovascular endothelial cells (HCEC) subjected to a 4 h in vitro ischemia (hypoxia + glucose deprivation) followed by a 4-24 h recovery express elevated levels of ICAM-1, IL-8, and MCP-1 mRNAs (semi-quantitative RT-PCR) and secrete increased amounts of the immunoreactive chemokines IL-8 and MCP-1 (ELISA). The ischemia-induced expression of ICAM-1 in HCEC, and the expression/release of IL-8 and MCP-1 in HCEC were abolished by the non-steroid anti-inflammatory drug, indomethacin (100-300 microM). The immunosuppressant cyclosporin A (50 microM) partially reduced the ischemia-stimulated IL-8 and MCP-1 secretion by HCEC. Both indomethacin and cyclosporin A also inhibited the ischemia-induced neutrophil chemotaxis elicited by HCEC media. The study indicates that in vitro ischemia augments the expression of adhesion molecules and leukocyte chemoattractants at the site of the BBB. This ischemic pro-inflammatory activation of HCEC may constitute a key event in initiating post-ischemic inflammation, and it can be suppressed by the anti-inflammatory drugs, indomethacin and cyclosporin A.
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PMID:Indomethacin and cyclosporin a inhibit in vitro ischemia-induced expression of ICAM-1 and chemokines in human brain endothelial cells. 1145 70


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