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)

The synthesis and the biological evaluation of a new family diterpenes are presented. The synthetic studies were inspired by the structural framework of acanthoic acid (1) and yielded a family of compounds that were evaluated as anti-inflammatory agents. Among them, compounds 2, 10, 12, and 16 exhibited a very low nonspecific cytotoxicity and inhibited the synthesis of TNF-alpha with greater than 65 % efficacy at low micromolar concentrations. Cytokine-specificity studies revealed that these compounds also inhibited the synthesis of the proinflammatory cytokines IL-1beta and IL-6, while inhibition of IL-1ra and IL-8 synthesis was marginal and only occurred at high concentrations. Further studies, through EMSA and Western blot analyses, indicated that these compounds decreased the extent of phosphorylation of IkappaBalpha; this suggests that they exert their anti-inflammatory profile by inhibiting NF-kappaB-mediated cytokine synthesis. These findings imply that these diterpenes represent promising leads for the development of novel anti-inflammatory agents.
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PMID:A new family of synthetic diterpenes that regulates cytokine synthesis by inhibiting IkappaBalpha phosphorylation. 1554 Feb 20

Helicobacter pylori infection and the cytokine-mediated inflammatory responses play important roles in gastric cancer pathogenesis. This case control study was conducted to assess the association between genetic polymorphisms in interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor alpha (TNFalpha), which are involved in H.pylori infection, and risk of gastric cancer. Genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 250 incident cases with gastric cancer and 300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. We found that the risk of gastric cancer was significantly elevated in subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence interval (CI) 1.27-3.21] or IL-10-1082 G (OR 2.02; 95% CI 1.24-3.29) or TNFalpha-308 AG (OR 1.81; 95% CI 1.04-3.14) genotype. An elevated risk of gastric cancer was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR 2.54; 95% CI 1.38-4.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.42-4.93). An increased OR was also suggested for IL-1B-31 and TNFalpha-238, but confidence intervals included the null value. There was no evidence of increased risk for any of the other polymorphisms evaluated. These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFalpha may play important roles in developing gastric cancer in the Chinese population.
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PMID:Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population. 1557 81

Fresh noma is a severe orofacial necrosis with an astonishingly rapid development. It is seen mainly in malnourished children less than 4 years old from developing countries. Cytokines play a central role in oral mucosal inflammation. We therefore studied the relevance of circulating cytokines to noma, and the key microorganisms associated with the lesion. Nigerian village children with acute noma (n=68) and their neighborhood village (n=63) as well as urban (n=45) counterparts of comparable age and free of overt infections were evaluated for serum cytokine levels by ELISA. Oral bacteria were studied by polymerase chain reaction. Evaluation of random cases of the village and noma children showed marked depletion (p<0.05 or 0.001) of the plasma antioxidant micronutrients (retinol, ascorbic acid, zinc) as well as albumin and blood hemoglobin in the latter, relative to the former group. Concentrations of the circulating, pro-inflammatory cytokines (IL-18, IL-6, IL-12, IL-8, IFN-gamma) and the soluble inhibitors (TNFR-p55, TNFR-p75 and IL-1ra) were significantly higher (p<0.01 or 0.001) in noma children than in the healthy urban children, but less so when compared to their neighborhood village counterparts. The increase in levels of the anti-inflammatory/regulatory cytokines (IL-4, IL-10 and TGF-beta) was less marked relative to the pro-inflammatory cytokines. Bacteria observed at the highest frequencies in noma lesions were P. intermedia (83%), T. forsythensis (83%), P. gingivalis (50%), C. rectus (50%) and T. denticola (50%). We conclude that noma is an immunopathological response to potent bacterial factors resulting in uncontrolled production of cytokines and possibly other, still unknown, inflammatory mediators.
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PMID:Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma). 1580 9

Disks consisting of macroporous nickel-titanium alloy (NiTi, Nitinol, Actipore) are used as implants in clinical surgery, e.g. for fixation of spinal dysfunctions. The morphological properties were studied by scanning electron microscopy (SEM) and by synchrotron radiation-based microtomography (SRmuCT). The composition was studied by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and energy-dispersive X-ray spectroscopy (EDX). The mechanical properties were studied with temperature-dependent dynamical mechanical analysis (DMA). Studies on the biocompatibility were performed by co-incubation of porous NiTi samples with isolated peripheral blood leukocyte fractions (polymorphonuclear neutrophil granulocytes, PMN; peripheral blood mononuclear leukocytes, PBMC) in comparison with control cultures without NiTi samples. The cell adherence to the NiTi surface was analyzed by fluorescence microscopy and scanning electron microscopy. The activation of adherent leukocytes was analyzed by measurement of the released cytokines using enzyme-linked immunosorbent assay (ELISA). The cytokine response of PMN (analyzed by the release of IL-1ra and IL-8) was not significantly different between cell cultures with or without NiTi. There was a significant increase in the release of IL-1ra (p<0.001), IL-6 (p<0.05), and IL-8 (p<0.05) from PBMC in the presence of NiTi samples. In contrast, the release of TNF-alpha by PBMC was not significantly elevated in the presence of NiTi. IL-2 was released from PBMC only in the range of the lower detection limit in all cell cultures. The material, clearly macroporous with an interconnecting porosity, consists of NiTi (martensite; monoclinic, and austenite; cubic) with small impurities of NiTi2 and possibly NiC(x). The material is not superelastic upon manual compression and shows a good biocompatibility.
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PMID:Morphological characterization and in vitro biocompatibility of a porous nickel-titanium alloy. 1594 45

Administration of endotoxin (LPS) in humans results in profound physiological responses, including activation of peripheral blood mononuclear cells and the release of inflammatory factors. The time course of the response of selected inflammatory proteins was examined in healthy subjects (n = 6) administered a single intravenous dose of the purified derivative of endotoxin (3.0 ng/kg). Microarray analysis demonstrated changes in the expression of a number of genes, which were confirmed in separate in vitro endotoxin stimulation experiments. Subsequent TaqMan analysis of genes of interest indicated time-dependent changes in the expression of many of these genes. This included pre-B cell enhancing factor, which was identified on microarray analysis as being markedly upregulated following endotoxin stimulation. Protein expression of the genes examined by TaqMan analysis was measured and demonstrated the appearance of tumor necrosis factor (TNF)-alpha and sTNF-R proteins in the plasma beginning within 1 h after dosing, followed by other cytokines/ inflammatory markers (e.g., IL-1ra, G-CSF, IL-6, IL-8, and IL-10) and suppressors of cytokine signaling (SOCS-1 and SOCS-3). In general, cytokine protein expression correlated well with gene expression; however, the temporal profile of expression of some genes did not correlate well with the protein data. For many of these proteins, the lack of correlation was attributable to alternate tissue sources, which were demonstrated on TaqMan analysis. Principal component analysis indicated that cytokines could be grouped according to their temporal pattern of response, with most transcript levels returning to baseline 24 h following endotoxin administration. The combination of cDNA microarray and TaqMan analysis to identify and quantify changes in gene expression, along with the analysis of protein expression, can be useful in investigating inflammatory and other diseases.
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PMID:Correlation of protein and gene expression profiles of inflammatory proteins after endotoxin challenge in human subjects. 1600 10

Muscle damage and perceived soreness following the 160-km Western States Endurance Run were related to changes in plasma cytokines and use of nonsteroidal anti-inflammatory drugs (NSAIDS). Subjects included 60 ultramarathoners (mean+/-SE, age 45.3 +/- 1.1 years) who finished the race in under 30 h (26.3 +/- 0.4 h). Blood samples were collected the morning prior to and immediately following the race, and subjects recorded muscle soreness during the week following the race using a 10-point Likert scale (DOMS). Seven plasma cytokines were measured including IL-6, IL-10, IL-8, IL-1ra, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1beta (MIP-1beta). Cytokine changes were compared between NSAID users and nonusers, and correlated with creatine phosphokinase (CPK) and DOMS. Significant increases were measured for all seven cytokines, with the greatest fold increases seen for IL-6 (125x), IL-10 (24x), and G-CSF (12x). CPK was correlated with changes in IL-6, G-CSF, IL-10, IL-1ra, and MCP-1 (r = .49-.68), (P < .001), but not IL-8 or MIP-1beta. DOMS averaged 7.1 +/- 0.3 the day after the race, and 5.0 +/- 0.3, 2.5 +/- 0.2, and 1.6 +/- 0.1 3 days, 5 days, and 7 days post-race, respectively, and each was correlated with CPK (r = .40-.63, P < .001) and changes in IL-6, G-CSF, IL-10, and MCP-1 (r = .28-.77, P < .05). A comparison of NSAID users (72% of athletes) and nonusers showed no differences in CPK or DOMS, but did reveal greater increases in five of seven cytokines in the NSAID users (P < .05). In conclusion, muscle damage in athletes competing in a 160-km race was significantly correlated with post-race DOMS and increases in five of seven cytokines. NSAID users did not experience a reduction in muscle damage or DOMS, but did have higher post-race plasma levels in five of seven cytokines.
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PMID:Muscle damage is linked to cytokine changes following a 160-km race. 1606 Nov 49

Chronic inflammation is one of the main underlying mechanisms in the development of coronary artery disease (CAD). We investigated the prognostic value of inflammatory markers for cardiac events occurring more than 6 months after percutaneous coronary intervention (PCI), i.e. late cardiac events, furthermore we investigated the temporal stability of these markers. Exhausted patients (234) recently treated by successful PCI were studied. Serum samples collected about 6 weeks after PCI (baseline), 6 and 18 months after baseline were analyzed for CRP, IL-6, tumour necrosis factor (TNF-alpha), IL-10, IL-1ra, IL-8 and neopterin. In the mean cardiac follow-up of 24 months, 25 late cardiac events occurred. Cox proportional hazards analysis was used to determine the prognostic value. Elevated concentrations of IL-6 at baseline and 6 months later increased the risk of late cardiac events (RR 3.9, CI 1.7-9.0, p 0.00 and RR 3.6, CI 1.6-8.5, p 0.00). Elevated concentrations of CRP and IL-10 at baseline also increased the risk of late cardiac events (RR 2.5, CI 1.1-5.7, p 0.04 and RR 2.5, CI 1.1-5.6, p 0.03) as did IL-1 receptor antagonist at 6 months (RR 2.6, CI 1.1-6.1, p 0.04). Temporal stability was high for most markers, but highest for IL-6. These results support the assumption that chronic inflammation is a pathophysiological mechanism in the development of CAD.
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PMID:Inflammatory markers predict late cardiac events in patients who are exhausted after percutaneous coronary intervention. 1615 7

The objective of this study was to analyze the pattern of the inflammatory response to heatstroke in an experimental baboon model with a view to identifying potential target for therapeutic interventions. Blinded analysis of plasma collected from 12 juvenile baboons (Papio hamadryas) in heatstroke was used. Eight anesthetized animals were heat-stressed in an incubator at 44 degrees C to 47 degrees C until rectal temperature was 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. We performed sequential measurement of cytokines. The rectal temperature on completion of heat stress was 42.5 degrees C +/- 0.0 degrees C and 43.3 degrees C +/- 0.1 degrees C in moderate and severe heatstroke, respectively. Heat stress elicited early, simultaneous release of anti-inflammatory cytokines and chemokines (IL-10, IL-1ra, sTNFr I and II, and IL-8). Circulating levels of IL-12p40 were significantly decreased, whereas TNFalpha, IL-1beta, and IL-4 were below the detection limit in all animals. No baboon survived severe heatstroke; there was neurological morbidity without mortality in moderate heatstroke. Nonsurvivors displayed significantly greater activity/alterations in inflammation markers than survivors. Sham-heated animals had no evidence of inflammation activation. These results show that heatstroke activates complex systemic inflammatory and regulatory responses associated with outcome. Further definition of this ambivalent response is needed before identification of target of successful modulation may become possible.
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PMID:Experimental heatstroke in baboon: analysis of the systemic inflammatory response. 1620 17

Host genetic susceptibility may influence gastric carcinogenesis caused by Helicobacter pylori infection. We aimed to clarify the relationship of interleukin (IL)-8 polymorphism with the risk of atrophic gastritis and gastric cancer. We examined IL-8 -251 T > A, IL-1B -511 C > T, and IL-1RN intron 2 polymorphisms in 252 healthy controls, 215 individuals with atrophic gastritis, and 396 patients with gastric cancer. We also investigated the effect of the IL-8 polymorphism on IL-8 production and histologic degree of gastritis in noncancerous gastric mucosa. Although no correlation was found in the analysis of the IL-1B and IL-1RN polymorphisms, IL-8 -251 A/A genotype held a higher risk of atrophic gastritis [odds ratio (OR), 2.35; 95% confidence interval (CI), 1.12-4.94] and gastric cancer (OR, 2.22; 95% CI, 1.08-4.56) compared with the T/T genotype. We also found that the A/A genotype increased the risk of upper-third location (OR, 3.66; 95% CI, 1.46-9.17), diffuse (OR, 2.79; 95% CI, 1.21-6.39), poorly differentiated (OR, 2.70; 95% CI, 1.14-6.38), lymph node (OR, 2.50; 95% CI, 1.01-6.20), and liver metastasis (OR, 5.63; 95% CI, 1.06-30.04), and p53-mutated (OR, 1.91; 95% CI, 1.13-3.26) subtypes of gastric cancer. The A/A and A/T genotypes were significantly associated with higher levels of IL-8 protein compared with the T/T genotype. Neutrophil infiltration score was significantly higher in the A/A genotype than in the T/T genotype. In conclusion, we showed that the IL-8 -251 T > A polymorphism is associated with higher expression of IL-8 protein, more severe neutrophil infiltration, and increased risk of atrophic gastritis and gastric cancer.
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PMID:Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. 1628 68

With a short lifespan and containing only few ribosomes and endoplasmic reticulum structures, neutrophils are thought to have a limited capacity for protein synthesis. We here show that peripheral blood polymorphonuclear neutrophils (PMN) are able react to stimulants with differential production of two interleukin (IL)-1 receptor antagonist (IL-1ra) isoforms, secreted IL-1ra (sIL-1ra) and the 16kDa intracellular form of IL-1ra (icIL-1ra3), as well as IL-8. Neutrophils of a high purity and with a low degree of preactivation upregulate mRNA and de novo synthesize protein of both IL-1ra variants and IL-8 in response to granulocyte-macrophage colony-stimulating factor and lipopolysaccharide. The cytokines are differentially regulated and distributed in two intracellular compartments. In comparison with peripheral blood mononuclear cells (PBMC), PMN produce distinctly more sIL-1ra but significantly less IL-8. This may indicate an anti-inflammatory role, enabling PMN to antagonize proinflammatory signals. It is therefore possible that PMN play an important role in immune regulation by counteracting a dysregulation of the inflammatory process.
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PMID:Differential synthesis of two interleukin-1 receptor antagonist variants and interleukin-8 by peripheral blood neutrophils. 1634 27


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