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 intestinal epithelium may serve as a nidus for inflammation that can cause local and systemic organ dysfunction. Relative to the adult, the immature intestine is exquisitely sensitive to inflammatory agents. Glutamine (Gln), an amino acid that is rapidly depleted during critical illness, modulates intestinal inflammation in vitro and in vivo. Here we relate Gln status to activation of the inhibitor of kappaB (IkappaB)/nuclear factor (NF)-kappaB signaling pathway in fetal-derived (H4) and adult (Caco-2) enterocytes. In the absence of Gln with or without LPS, H4 cells expressed more interleukin (IL)-8) than Caco-2 cells. Gln supplementation partially prevented the LPS-induced elevation of IL-8 in both cell types. IkappaBalpha was significantly decreased in both H4 and Caco-2 cells with Gln deprivation, and this was followed by an increase in NF-kappaB p65 in the nucleus. DNA binding of NF-kappaB was increased in both H4 and Caco-2 cells with Gln deprivation. IkappaBalpha phosphorylation was not altered by Gln status in either H4 or Caco-2 cells. Proteasomal inhibition after Gln depletion in Caco-2 cells was associated with an increase in the IkappaB-ubiquitin complex, but a decrease in complex formation in H4 cells, indicating that Gln deprivation alters IkappaBalpha through a pathway that differs from Caco-2 cells. We speculate that a reduced capacity of the immature enterocyte (H4) to respond to Gln deprivation with increased synthesis of IkappaBalpha rather than increased proteolysis as seen in the Caco-2 cells is the underlying mechanism.
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PMID:Glutamine modulates LPS-induced IL-8 production through IkappaB/NF-kappaB in human fetal and adult intestinal epithelium. 1567 Dec 21

We recently showed that oligomerization of CD40 molecules on cell surface leads to disulfide-linked CD40/CD40 dimer formation, an event that is necessary for CD40-induced B7-2 expression in human B cells. Here, we demonstrate that CD40/CD40 dimers formation also occurs in different cell types such as T24 bladder cancer cells and CD40-transfected HEK 293 cells. Disulfide bonds mediate the formation of CD40/CD40 homodimers in CD40-activated cells. To determine the potential residue(s) involved in disulfide bonds formation and subsequent CD40-induced IL-8 expression, we generated a CD40 mutant in which the extracellular cysteine 6 was replaced by a glutamine (CD40-C6Q). CD40-induced IL-8 mRNA expression and protein synthesis were studied in stably transfected HEK 293 cells that were sorted out along with similar levels of expression of wild type (CD40-WT) and CD40-C6Q molecules. In contrast to cells expressing CD40-WT protein, disulfide-linked CD40/CD40 dimer formation was completely abolished in HEK 293 cells expressing CD40-C6Q proteins. Abolishment of disulfide-linked CD40/CD40 dimers in these transfected cells was sufficient to inhibit CD40-induced mRNA expression and secretion of IL-8. This study identifies the extracellular cysteine 6 of CD40 molecules as a potential molecular target to disrupt the expression of CD40-induced pro-inflammatory cytokines by epithelial cells.
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PMID:Requirement of the extracellular cysteine at position six for CD40/CD40 dimer formation and CD40-induced IL-8 expression. 1582 65

This study evaluated whether glutamine (GLN) concentration was related to endothelial surface molecule expression and the migration of polymorphonuclear neutrophils (PMNs) through endothelial cells (ECs) stimulated by arsenic. Human umbilical vein endothelial cells (HUVECs) and PMNs were treated with different GLN concentrations (0, 300, 600 and 1000 microM) for 24 h. After that, we stimulated HUVECs for 3 h with 0.5 microM arsenic, and PMNs were allowed to transmigrate to ECs for 2 h. HUVEC surface expressions of cell adhesion molecules and integrin (CD11b) and interleukin (IL)-8 receptor expressions on PMNs were measured. The transendothelial migration of PMNs was also analyzed. The results showed that cell adhesion molecule (CAM) and integrin expressions in arsenic groups were higher than in those without arsenic. Among the arsenic groups, the expression of CAMs on ECs and CD11b, and IL-8 receptor on PMNs was lowest with 0 microM compared with the other GLN concentrations. Vascular CAM-1 on ECs and CD11b on PMN expression were higher with 300 microM than with 600 and 1000 microM GLN. IL-8 secretions from ECs and PMNs were higher with 300 muM than with 600 and 1000 microM GLN, and this was consistent with the expression of the IL-8 receptor on PMNs. Polymorphonuclear neutrophil transmigration was significantly higher with 300 muM GLN than with other GLN concentrations. These results suggest that ECs and PMNs were activated after arsenic stimulation. Cell adhesion molecule expressions on ECs and PMNs were suppressed in the absence of GLN. A low GLN concentration comparable to catabolic conditions resulted in higher adhesion molecule expression and greater transendothelial migration of neutrophils. Glutamine administration at levels similar to or higher than physiological concentrations reduced IL-8 and adhesion molecule expression; PMN transmigration was also decreased after stimulation with arsenic.
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PMID:Effects of glutamine on adhesion molecule expression and leukocyte transmigration in endothelial cells exposed to arsenic. 1608 78

This study investigated the effect of glutamine (GLN) concentration on surface molecule expression on endothelial cells (ECs) and leukocytes and the transendothelial migration of polymorphonuclear neutrophils (PMNs) through ECs stimulated by plasma or peritoneal drain fluid (PDF) from a surgical patient. Human umbilical vein ECs (HUVECs) and PMNs from normal subjects were treated with different concentrations (0, 300, 600, and 1000 micromol/L) of GLN for 24 h. After that, HUVECs were stimulated for 3 h with plasma or PDF from a patient who had undergone abdominal surgery, and PMNs were allowed to transmigrate through ECs for 2 h. HUVEC surface expression of cell adhesion molecules and integrin (CD11b) and interleukin (IL) 8 receptor expression on PMNs were measured by flow cytometry. PMNs transmigrating through ECs were also analyzed. The results showed that cell adhesion molecule and integrin expressions in PDF groups were higher than those in control groups. Among the PDF groups, cellular adhesion molecule expressions on ECs and CD11b expression on PMNs were lower with 600 and 1000 micromol/L than with 300 micromol/L GLN. IL-8 secretions from ECs and PMNs were higher with 300 and 600 micromol/L than with 1000 micromol/L GLN, and this was consistent with the expression of the IL-8 receptor on PMNs. PMN transmigration was significantly higher with 300 micromol/L GLN than with the other GLN concentrations. HUVECs stimulated by plasma from surgical patient had the similar effects on surface molecule expression as PDF; however, the influences were not so obvious as shown in PDF stimulation. The results of this in vitro study suggest that ECs and PMNs were activated after patient's plasma or PDF stimulation. A low GLN concentration comparable to catabolic conditions resulted in higher adhesion molecule expression and greater transendothelial migration of neutrophils. GLN administration at levels similar to or higher than physiological concentrations reduced IL-8 and adhesion molecule expression, and PMN transmigration was also decreased after stimulation with plasma or PDF from a surgical patient.
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PMID:Effect of glutamine on cellular adhesion molecule expression and leukocyte transmigration in endothelial cells stimulated by plasma or peritoneal drain fluid from a surgical patient. 1655 54

Glutamine, the most abundant amino acid in the human body, plays several important roles in the intestine. Recent studies showed that glutamine regulates protein metabolism and intestinal inflammation among other mechanisms by reducing proinflammatory cytokine release. Because regulation of the inflammatory response was shown to be linked to proteolysis regulation, we hypothesized that glutamine pretreatment could act on IL-8 production in human intestinal epithelial cells through the regulation of inhibitor kappaB (IkappaB) ubiquitination. The HCT-8 cells were pretreated for 24 h with 0.6, 2, or 10 mmol/L glutamine. IL-8 concentration and IkappaB (free and ubiquitinated) expressions were assessed by ELISA and immunoblotting, respectively. A pretreatment with 10 mmol/L glutamine decreased IL-8 production under both basal and proinflammatory conditions (both P < 0.05). In the presence of a proteasome inhibitor (MG132), the ubiquitin-IkappaBalpha complex expression was not significantly modified by glutamine under basal conditions but decreased significantly under proinflammatory conditions (P < 0.05). After the addition of 10 mmol/L of glutamine, the free IkappaBalpha expression increased under basal and stimulated conditions (both P < 0.05). A glutamine pretreatment of 10 mmol/L did not affect ubiquitin expression or proteasome activity. This study indicates that glutamine pretreatment may reduce the intestinal inflammatory response by limiting the proteolysis of IkappaBalpha.
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PMID:Glutamine pretreatment reduces IL-8 production in human intestinal epithelial cells by limiting IkappaBalpha ubiquitination. 1670 4

Understanding how the various host cells respond to probiotic bacteria in vitro may provide important insight into elaborate immune responses triggered by beneficial bacteria. The aim of this study was to investigate the detailed pattern of the mRNA expression of cytokines (IL-1beta, IL-8, TNF-alpha and TGF-beta) in head kidney (HK) leucocytes and gut cells isolated from rainbow trout (Oncorhynchus mykiss Walbaum) after co-culturing with live probiotics. HK leucocytes and gut cells adjusted to 5 x 10(6) and 2 x 10(6) ml(-1), respectively, in L-15 medium containing 25% decomplemented FCS and 300 mg l(-1) L-glutamine were co-cultured with Carnobacterium maltaromaticum B26 and C. divergens B33 at an multiplicity of infection of 25 for 6 and 12 h. Quantitative real-time reverse transcriptase polymerase chain reaction using SYBR Green I was employed to determine the mRNA expression of studied genes. Although neither probiotic strains significantly induced mRNA of the cytokines in gut cells, expression ratios of IL-1beta and TNF-alpha of HK cells were significantly higher, suggesting that these bacteria can stimulate innate immunity in rainbow trout.
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PMID:Cytokine expression in leucocytes and gut cells of rainbow trout, Oncorhynchus mykiss Walbaum, induced by probiotics. 1701 Oct 45

Enteral arginine supplementation in the critically ill has become a matter of controversy. In this study, we investigated effects of the addition of 0.4 and 1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte layer integrity, and amino acid transport. In this model, a monolayer of intestinal epithelial cells (Caco-2) separated compartments with nonpathogenic Escherichia coli and mononuclear leukocytes. Activation of enterocytes and leukocytes was assessed by the measurement of nitric oxide, TNF-alpha, IL-6, IL-8, IL-10, and IFN-gamma. Further outcomes were the transepithelial flux of 22 amino acids, their catabolism, and the integrity of the enterocyte layer assessed as permeability of fluorescein dextran (M(r) 4400). Bacterial stimulation of intestinal epithelial cells enhanced the basolateral concentration of nitric oxide and all cytokines measured. Supplementation with arginine did not affect epithelial integrity, production of any of the cytokines investigated, or the amount of nitric oxide. The amino acid used primarily by nonstimulated intestinal epithelial cells cocultured with leukocytes was glutamine. Activation of IEC with bacteria significantly enhanced the catabolism of serine, asparagine, and lysine, and reduced glutamine catabolism. Addition of arginine increased ornithine formation and moderately reduced transepithelial transport of methionine and other amino acids. Hence, arginine supplementation does not interfere with inflammation-associated cross-talk between human enterocytes and leukocytes. Because it also does not seem to affect the integrity of enterocyte layers, a detrimental role of arginine during septic-like conditions seems unlikely.
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PMID:Arginine does not exacerbate markers of inflammation in cocultures of human enterocytes and leukocytes. 1718 9

The intestines are an important organ responsible for nutrient absorption, metabolism and recognition of food signals. The organ also acts as a physical and biological barrier against harmful substances including food pathogens and environmental chemicals. Food-derived peptides with a variety of physiological functions have been discovered in the past several decades. Although dietary peptides would mostly be hydrolyzed by digestive enzymes in the intestinal tract, possibly losing their biological functions during this step, some could be absorbed intact and act in their target organs. The intestines are also one of the targets for functional peptides. The intestine-modulatory peptides can be classified into two categories: (1) peptides that express their functions in the intestinal tract and (2) peptides that modulate intestinal epithelial cell functions. The 1(st) group includes peptides that regulate the intestinal absorption of nutrients. Enhancing mineral absorption by casein phosphopeptides, and suppressing dietary cholesterol absorption by soybean peptides are typical examples. The 2(nd) group includes such glutamine-containing peptides as Ala-Gln that show interesting properties in preventing and/or repairing damage caused by oxidative stress and inflammatory reactions. We have found that carinosine (beta-Ala-His) suppressed the secretion of such inflammatory cytokines as IL-8 in human intestinal epithelial cells, suggesting its anti-inflammatory function in the intestines. Peptides that modulate such intestinal immune functions as secretory IgA production and cytokine secretion, and opioid peptides regulating intestinal motility are also included in this group. These intestine-modulatory peptides would be useful as ingredients of future functional foods to prevent lifestyle-related diseases and promote gut health.
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PMID:Food-derived peptides and intestinal functions. 1743 Jan 88

Glutamine (Gln) and arginine (Arg) are conditionally essential amino acids with immunomodulatory properties. The aim of the study was to assess the effects of Gln and Arg alone or in combination on cytokine release by cultured colonic biopsies from patients with active Crohn's disease (CD). Ten consecutive patients [mean (range) age 26 (18-39) y] with active colonic CD (mean CD activity index: 383.7 +/- 129.8) were prospectively included in the study. Eight colonic biopsies were obtained via a colonoscopy and incubated during 18 h with low (physiological) or high (pharmacological) doses of Arg (0.1 or 2 mmol/L designated as Arg(low) or Arg(high), respectively) and Gln (0.6 or 10 mmol/L designated as Gln(low) or Gln(high), respectively). The concentrations of cytokines [interleukin (IL)-4, IL-10, IL-8, IL-6, tumor necrosis factor-alpha (TNFalpha), IL-1beta, interferon-gamma) were assessed by ELISA, and nitric oxide (NO) production was evaluated by Griess assay. Nuclear factor (NF)-kappaB p65 subunit, inhibitor of NFkappaB-alpha, and p38 mitogen-activated protein kinase (MAPK) were assessed by immunoblotting. Arg(high)/Gln(high) decreased the production of TNFalpha, IL-1beta, IL-8, and IL-6 (each P < 0.01). Arg(low)/Gln(high) decreased IL-6 and IL-8 production (both P < 0.01), whereas Arg(high)/Gln(low) did not affect cytokine and NO production. Arg(low)/Gln(high) and Arg(high)/Gln(high) decreased NF-kappaB p65 subunit expression, whereas p38 MAPK was decreased only by Arg(high)/Gln(high). Combined pharmacological doses of Arg and Gln decreased TNFalpha and the main proinflammatory cytokines release in active colonic CD biopsies via NF-kappaB and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD.
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PMID:Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn's patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways. 1902 76

Hyperglycemia and insulin resistance are common in many critically ill patients. Hyperglycemia increases the production of reactive oxygen species in cells, stimulates the production of the potent proinflammatory cytokines IL-8 and TNF-alpha, and enhances the expression of haem oxygenase-1, an inducible stress protein. It has been shown that administration of insulin and the semi-essential amino acid glutamine have been beneficial to the septic patient. The aim of our study is to test whether these two molecules, glutamine and insulin used in combination attenuate the proinflammatory responses in endothelial cells which have been triggered by hyperglycaemia. Our results demonstrate that a combination of insulin and glutamine are significantly more effective in reducing the expression of IL-8, TNF-alpha and HO-1 than insulin or glutamine alone.
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PMID:The oxidative stress of hyperglycemia and the inflammatory process in endothelial cells. 1926 7


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