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)

Recruitment of neutrophils to the lung is a sentinel event in acute lung inflammation. Identifying mechanisms that regulate neutrophil recruitment to the lung may result in strategies to limit lung damage and improve clinical outcomes. Recently, the renin angiotensin system (RAS) has been shown to regulate neutrophil influx in acute inflammatory models of cardiac, neurologic, and gastrointestinal disease. As a role for the RAS in LPS-induced acute lung inflammation has not been described, we undertook this study to examine the possibility that the RAS regulates neutrophil recruitment to the lung after LPS exposure. Pretreatment of mice with the angiotensin-converting enzyme (ACE) inhibitor enalapril, but not the anti-hypertensive hydralazine, decreased pulmonary neutrophil recruitment after exposure to LPS. We hypothesize that inhibition of LPS-induced neutrophil accumulation to the lung with enalapril occurred through both an increase in bradykinin, and a decrease in angiotensin II (ATII), mediated signaling. Bradykinin receptor blockade reversed the inhibitory effect of enalapril on neutrophil recruitment. Similarly, pretreatment with bradykinin receptor agonists inhibited IL-8-induced neutrophil chemotaxis and LPS-induced neutrophil recruitment to the lung. Inhibition of ATII-mediated signaling, with the ATII receptor 1a inhibitor losartan, decreased LPS-induced pulmonary neutrophil recruitment, and this was suggested to occur through decreased PAI-1 levels. LPS-induced PAI-1 levels were diminished in animals pretreated with losartan and in those deficient for the ATII receptor 1a. Taken together, these results suggest that ACE regulates LPS-induced pulmonary neutrophil recruitment via modulation of both bradykinin- and ATII-mediated pathways, each regulating neutrophil recruitment by separate, but distinct, mechanisms.
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PMID:Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccharide-induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways. 1708 41

C-reactive protein (CRP) is the prototypic marker of inflammation and a strong predictor of cardiovascular events in humans. There are questions regarding the validity of the biological effects reported for CRP, in spite of adherence to rigorous control measures minimizing endotoxin [lipopolysaccharide (LPS)] contamination in these in vitro studies. In this study, we addressed the key question of endotoxin contamination in CRP preparations using Toll-like receptor 4 (TLR4) knockdown endothelial cells. Human aortic endothelial cells (HAECs) transfected with prevalidated TLR4 small interfering RNA (siRNA) and scrambled siRNA controls were challenged with pleural fluid-derived CRP or LPS for 12-16 h. Secreted interleukin-6 (IL-6), IL-1beta, IL-8, and plasminogen activator inhibitor-1 (PAI-1) levels and endothelial Nitric oxide synthase (eNOS) activity were determined. TLR4 knockdown in HAECs significantly decreased LPS-induced IL-1beta, IL-6, and IL-8, whereas the stimulatory effects of CRP were similar in both scrambled control and TLR4 knockdown cells. Furthermore, CRP significantly stimulated PAI-1 levels in both control and TLR4-transfected cells and inhibited eNOS activity, whereas LPS effects were negated in TLR4-transfected cells. The data presented cogently demonstrate and further confirm that the biological effects of CRP on HAECs are independent of LPS and thus are attributable to native protein per se. This is the first study to positively authenticate the significance of earlier in vitro reports on CRP biological effects.
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PMID:The biological effects of CRP are not attributable to endotoxin contamination: evidence from TLR4 knockdown human aortic endothelial cells. 1715 93

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the western world with its incidence increasing lately in developing countries. Several lines of evidence support a role for inflammation in atherogenesis. Hence, dietary micronutrients having antiinflammatory properties may have a potential beneficial effect with regard to CVD. Vitamin E is a potent antioxidant with antiinflammatory properties. It comprises eight different isoforms: four tocopherols (T) (alpha, beta, gamma, and delta) and four tocotrienols (T3) (alpha, beta, gamma, and delta). A wealth of data is available for the preventive efficacy of alpha-T. alpha-T supplementation in human subjects and animal models has been shown to be antioxidant and antiinflammatory in terms of decreasing C-reactive protein (CRP) and release of proinflammatory cytokines, the chemokine IL-8 and PAI-1 levels especially at high doses. gamma-T is effective in decreasing reactive nitrogen species and also appears to have antiinflammatory properties; however, there are scanty data examining pure gamma-T preparations. Furthermore, tocotrienols (alpha and gamma) also have implications for prevention of CVD; however, there are conflicting and insufficient data in the literature with regards to their potency. In this chapter, we have gathered recent emerging data on alpha-T specifically and also have given a composite view of gamma-T and tocotrienols especially with regards to their effect on inflammation as it relates to CVD.
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PMID:Vitamin E: inflammation and atherosclerosis. 1762 88

It is desirable in the treatment of IgA nephropathy (IgAN) to prevent the downstream events after the immune response has involved the glomerulus. We and others observed that IgA itself could directly activate mesangial cells to produce monocyte chemotactic peptide-1 (MCP-1), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) and this was suppressed by the treatment with steroid or angiotensin receptor blocker (ARB). It was shown in mesangial cells that the increased expression of TGF-beta and plasminogen activator inhibitor-1 induced by angiotensin II was suppressed by the treatment with ARB, calcium channel blocker (CCB), spironolactone or peroxisome proliferator-activated-receptor-gamma (PPAR-gamma) agonist. It was well known in the patients with IgAN that renal or intraglomerular TGF-beta1 gene expression was increased. Interestingly, treatment with angiotensin-converting enzyme (ACE) inhibitors induced significantly lower renal TGF-beta1 gene expression in patients with IgAN. It was reported in several studies that urinary levels of IL-6, IL-8, MCP-1 or TGF-beta were increased in patients with IgAN. The increase was suppressed by the treatment with steroid, ARB or ACE inhibitor. More effective agents are necessary to ameliorate pathogenetic abnormalities and so to prevent the progression of IgAN.
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PMID:Effects of therapeutic agents on the inflammatory and fibrogenic factors in IgA nephropathy. 1799 24

Adipokines, soluble mediators produced by adipocytes, may link adipose tissue to the inflammatory, metabolic, and immune dysregulation that characterize many obesity-related diseases. The stability of plasma adipokine levels within individuals, their seasonal variability, intercorrelations, and relationships to well-established measures of adiposity are incompletely defined. We measured levels of 12 adipokines [interleukin 1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), leptin, adiponectin, hepatocyte growth factor (HGF), and resistin] in four seasonal random plasma samples of 48 male participants of a population-based cohort study. The representativeness of single measurements was assessed by correlating the adipokine levels of a single, random sample with the mean levels from the remaining three samples using a bootstrap approach and using intra-class correlation coefficients (ICC). Spearman correlations between adipokine levels, age, body mass index (BMI), and waist-to-hip ratio (WHR) were estimated. Correlations between plasma adipokine levels from one random sample and the mean of the remaining three seasonal samples ranged from 0.57 to 0.89. Over the 1-year study period, the ICCs for adipokine levels ranged from 0.44 (PAI-1) to 0.83 (HGF). IL-8, MCP-1, and resistin levels were positively associated with age; HGF and PAI-1 levels were correlated with BMI and WHR. This study suggests that adipokine levels in a single blood sample may be useful biomarkers of inflammation in population-based studies of obesity-related disease.
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PMID:Intra-individual variation of plasma adipokine levels and utility of single measurement of these biomarkers in population-based studies. 1800 38

Interleukin-8 (IL-8), a member of the CXC chemokine family, plays an important role in the modulation of multiple biological functions in endothelial cells containing the receptors CXCR1 and CXCR2. It has previously been shown that IL-8 directly enhances endothelial cell survival, and stimulates the production of matrix metalloproteinases, which in turn regulates angiogenesis. However, its role in the regulation of the production of vasoactive substances in endothelial cells is less well defined. In this study, we investigate the effects of IL-8 on the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, we also study the effects of IL-8 on the production of vasodilator, vasoconstrictor and fibrinolytic factors in these cells. The results show that recombinant IL-8 (50-200ng/ml) induces neither HUVEC proliferation nor nitric oxide (NO) release. However, it significantly increases the production of endothelin-1 (ET-1) in a concentration-dependent manner. Furthermore, incubation of endothelial cells with IL-8 (200ng/ml) up-regulates the plasminogen activator inhibitor-1 (PAI-1) in HUVECs, while it down-regulates the tissue plasminogen activator (t-PA). These findings suggest that IL-8 offsets the balance between endothelial vasoconstrictors and vasodilators. Furthermore, IL-8 also leads to an imbalance between PAI-1 and t-PA, which causes the ECs to become procoagulative and hypofibrinolytic.
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PMID:IL-8 induces imbalances between nitric oxide and endothelin-1, and also between plasminogen activator inhibitor-1 and tissue-type plasminogen activator in cultured endothelial cells. 1802 2

Abnormal distribution of plasma fatty acids and increased inflammation are prominent features of metabolic syndrome. We tested whether these components of metabolic syndrome, like dyslipidemia and glycemia, are responsive to carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an increased proportion of serum total n-6 PUFA, mainly attributed to a marked increase in arachidonate (20:4n-6), while its biosynthetic metabolic intermediates were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid ratio also increased sharply. Total saturated fatty acids and 16:1n-7 were consistently decreased following the VLCKD. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3 are commonly viewed as pro-inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory proteins. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.
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PMID:Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. 1804 94

The aim of the study was to evaluate the interactions of Permacol, Prolene mesh, Surgisis Gold, and Alloderm with human mesothelial cells in vitro. The capacity of primary human mesothelial cells to adhere to the surface of Alloderm, Surgisis Gold, Prolene mesh, and Permacol as well as support the proliferation and viability of the seeded cells was determined. Production of antifibrinolytic, fibrinolytic, and inflammatory mediators (IL-8, TPA, MMP-1, PAI-1, and TGF-beta) was assessed over an 8-day period. The adhesive nature of the implantable materials was determined by assessment of the strength of any fibrin clots formed between two surfaces of each implant material. Surgisis Gold and Permacol were capable of supporting the attachment and proliferation of primary human mesothelial cells and maintaining viability over an 8-day culture period. Mesothelial cells were shown to have covered the surface of Permacol and Surgisis Gold in a monolayer. The viability of cells cultured on Permacol was significantly greater than the other implant materials tested. Mesothelial cells cultured on Permacol or Surgisis were shown to be producing high levels of fibrinolytic compounds and low levels of antifibrinolytic and inflammatory mediators. Alloderm was shown to produce high levels of IL-8 and antifibrinolytic mediators when compared with the other implantable materials. Permacol was shown to be an unreliable surface for clot formation in vitro and any clots formed were shown to be significantly weaker than the clots produced between two surfaces of tissue culture plastic, Prolene mesh, Alloderm, and Surgisis Gold. This in vitro study indicated that Permacol and Surgisis Gold supported the growth and fibrinolytic activity of human mesothelial cells; however, Permacol was shown to be superior in this respect.
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PMID:Investigation of the antiadhesive properties of human mesothelial cells cultured in vitro on implantable surgical materials. 1854 80

Senescence is an irreversible growth arrest with important physiological implications as it contributes to tumour suppression and may have a role in aging. During senescence, cells suffer profound phenotypic changes affecting amongst others cell morphology and chromatin structure. Senescent cells also undergo significant transcriptional changes, such as the increased production of a plethora of different secreted factors, which are the basis of the so-called senescence-associated secretory phenotype. While some of these factors have been previously shown to possess different pro-tumorigenic activities, we recently demonstrated that the secretion of CXCR2-binding chemokines (such as IL-8 or GROalpha) by senescent cells contribute to reinforce senescence via activation of the p53 pathway. Importantly, our data adds to that presented by several groups suggesting that also other factors secreted during senescence (such as PAI-1, IGFBP-7 or IL-6) contribute to the senescent response. Here, we discuss our findings in the context of the emerging role for secreted factors in regulating senescence through paracrine and/or autocrine mechanisms.
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PMID:Control of senescence by CXCR2 and its ligands. 1883 63

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into lineages of mesenchymal tissues that are currently under investigation for a variety of therapeutic applications. The purpose of this study was to compare cytokine gene expression in MSCs from human placenta, cord blood (CB) and bone marrow (BM). The cytokine expression profiles of MSCs from BM, CB and placenta (amnion, decidua) were compared by proteome profiler array analysis. The cytokines that were expressed differently, in each type of MSC, were analyzed by real-time PCR. We evaluated 36 cytokines. Most types of MSCs had a common expression pattern including MIF (GIF, DER6), IL-8 (CXCL8), Serpin E1 (PAI-1), GROalpha(CXCL1), and IL-6. MCP-1, however, was expressed in both the MSCs from the BM and the amnion. sICAM-1 was expressed in both the amnion and decidua MSCs. SDF-1 was expressed only in the BM MSCs. Real-time PCR demonstrated the expression of the cytokines in each of the MSCs. The MSCs from bone marrow, placenta (amnion and decidua) and cord blood expressed the cytokines differently. These results suggest that cytokine induction and signal transduction are different in MSCs from different tissues.
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PMID:Comparison of cytokine expression in mesenchymal stem cells from human placenta, cord blood, and bone marrow. 1965 31


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