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)

Carnosine (beta-Ala-L-His) is known to have the physiological functions of an antioxidant. Although dietary carnosine is thought to be absorbed across intestinal epithelial cells, the mechanism for this absorption is not yet well understood and its function in the intestinal tract is also obscure. The intestinal transport of carnosine was characterized in the present study by using human intestinal Caco-2 cells, and its physiological function in these cells was further examined. The carnosine uptake was proton-dependent, being activated by lowering the apical pH value. Its uptake was significantly inhibited by other dipeptides, whereas it was not inhibited by other amino acids. These characteristics of the carnosine uptake strongly suggest its transport into the cells via peptide transporter 1 (PepT1). Since carnosine has antioxidative activity, we studied its effect on the H2O2-induced secretion of inflammatory cytokines in Caco-2 cells. The H2O2 induced increase in IL-8 secretion was inhibited by a pretreatment with carnosine for 3 h, this inhibition being presented in a dose-dependent manner. These results suggest that carnosine had a protective effect against oxidative stress in intestinal epithelial cells.
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PMID:Characterization of carnosine uptake and its physiological function in human intestinal epithelial Caco-2 cells. 1563 Feb 34

Severe acute pancreatitis is a clinical entity that can develop into multiple organ failure (MOF), and still has a poor prognosis. It is generally agreed that excessive humoral mediators such as pro-inflammatory cytokines play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP). Furthermore, it has been reported that continuous hemodiafiltration (CHDF) can remove the excess humoral mediators during the hypercytokinemic state of systemic inflammatory response syndrome (SIRS). We experienced a case of severe acute pancreatitis induced by alcohol abuse, on whom we performed cytokine apheresis. The patient was a 46 year-old male. He received 14 cytokine apheresis procedures, for about 4 hours in each session, using a CTR-001 direct hemoperfusion (DHP) cartridge. His serum levels of pro-inflammatory cytokines such as interleukin-6 (IL-6; 1649.1+/-667.1-1257.1+/-489.4 pg/mL, P=0.013) decreased significantly after the CTR-001 procedures. However tumor necrosis factor-alpha (TNF-alpha) (26.2+/-1.7-24.3+/-1.9 pg/mL, P=0.087), IL-1beta (6.1+/-2.9-3.49+/-1.1 pg/mL, P=0.477), IL-8 (192.5+/-33.4-229.5+/-51.8 pg/mL, P=0.754) and IL-10 (14.4+/-2.7-14.0+/-1.9 pg/mL, P=0.726) did not decrease statistically. Therefore, we conclude that in this case, cytokine apheresis using a CTR-001 cartridge was effective for reducing the pro-inflammatory cytokines during severe acute pancreatitis.
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PMID:A case of severe acute pancreatitis treated with CTR-001 direct hemoperfusion for cytokine apheresis. 1607 84

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

The major surface protein (MspTL) of Treponema lecithinolyticum, associated with periodontitis and endodontic infections, has been reported to induce proinflammatory mediators such as intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-1beta, IL-6 and IL-8. The purpose of this study was to examine the role of MspTL in cell adhesion/migration and to identify its proinflammatory domains. Using the human monocytic cell line THP-1 and human dermal microvascular endothelial cells (HMEC-1), it was demonstrated that MspTL increased adhesion of monocytes to endothelial cells and transendothelial migration. To analyse the proinflammatory domains of the protein, four gene constructs covering different regions of MspTL were designed and expressed in Escherichia coli using the expression vector pQE-30. Histidine-tagged recombinant proteins were purified using Ni-NTA agarose and polymyxin B agarose to remove LPS contamination. Recombinant truncated polypeptides were assessed for the ability to induce ICAM-1 and proinflammatory factors in THP-1 cells by real-time RT-PCR and ELISA. Of the four polypeptides, the one spanning the N-terminal 86 amino acids significantly induced ICAM-1, IL-1beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), cyclooxygenase (COX)-2, and prostaglandin E2 (PGE2). The results indicate that MspTL may induce cell adhesion and inflammation via its N-terminal region.
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PMID:Mapping of the proinflammatory domains of MspTL of Treponema lecithinolyticum. 1766 Apr 3

Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and inflammatory properties. Chemokines control mast cell infiltration in several inflammatory diseases, including stress and neurological dysfunctions. Using isolated human umbilical cord blood-derived cultured mast cells (HUCMC) from hematopoietic stem cells CD34+, mast cells were immunologically activated with anti-IgE at concentrations of 1, 5, 10 and 20 microg/ml leading to the dose-dependent production of IL-8 (p < 0.05). The increase in IL-8 mRNA expression was also noted when the cells were treated with anti-IgE at 10 microg/ml for 6 h. Immunologically activated HUCMC provoked the generation of tryptase in a dose- and time-dependent manner. We also found increased histidine decarboxylase (HDC) expression in activated HUCMC after 6 h of incubation, a rate-limiting enzyme responsible for the generation of histamine from histidine. Taken together, these results confirm that anti-IgE-activated mast cells release inflammatory mediators including CXCL8, a CXC chemokine which regulates several biological effects of mast cells, e.g. chemoattraction, and possibly causes cell arrest.
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PMID:Expression and secretion of CXCL8 (IL-8), release of tryptase and transcription of histidine decarboxylase mRNA by anti-IgE-activated human umbilical cord blood-derived cultured mast cells. 1771 57

The protective effects of amino acids against H 2O 2-induced oxidative stress were investigated in an in vitro assay using human intestinal epithelial cells. Caco-2 cells were pretreated with amino acids (1, 2, and 5 mM) for 2 h and then stimulated with 1 mM H 2O 2 for 6 h. The secretion of IL-8, a proinflammatory mediator, was determined by ELISA as an indicator of tissue oxidative stress. The inhibition of H 2O 2-induced IL-8 secretion from Caco-2 cells was observed by pretreatment with Cys, Val, Ile, Leu, Trp, His, Lys, and Ala. Cys enhanced glutathione (GSH) biosynthesis enzyme activity and increased cellular GSH levels. Branched-chain amino acids such as Val, Ile, and Leu elevated activities of GSH S-transferase (GST) and catalase. Trp, His, and Lys caused increases in GST activity. Ala enhanced GSH reductase activity. These data suggest that specific amino acids exert protective effects against tissue oxidative stress in intestinal epithelial cells based on the structure.
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PMID:Antioxidative activity of amino acids on tissue oxidative stress in human intestinal epithelial cell model. 1788 54

A 75-year-old previously healthy man presented for elective resection of rectal cancer under general anesthesia. Six days before the operation, he had a high-grade fever, and elevated leukocyte count and C-reactive protein concentration, but this was resolved by an intravenous antibiotic. His condition was well controlled before the operation. Soon after the operation started, severe hypoxemia emerged, with low arterial pressure. Fiberoptic bronchoscopy demonstrated a massive amount of plasma-like edema fluid; the total amount of suctioned fluid was approximately 800 ml at the end of the surgery. This acute pulmonary edema appeared to be due to increased permeability rather than pulmonary congestion as indicated by chest radiography, pulmonary artery occlusion pressure, echocardiogram, and the protein-rich edema fluid. Elevated concentrations of the proinflammatory cytokines, interleukin (IL)-6 and IL-8, in both plasma and the pulmonary edema fluid, suggested a possible role of systemic and pulmonary inflammation in the development of this acute pulmonary capillary leak. According to the "two-hit" hypothesis, the bacterial infection preceding the operation may have primed the immune cells, and the following surgical stress may have then triggered rapid progression of acute respiratory distress syndrome. We should keep in mind that, especially following sepsis, sudden massive pulmonary capillary leak can occur during elective surgery, even though the patient's condition is well controlled.
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PMID:Acute pulmonary capillary leak syndrome during elective surgery under general anesthesia. 1830 21

The role of cytokines, their putative transporters, and other acute phase reactants was studied in 17 men aged 57.2 +/- 9.6 yr with microfocal myocardial infarction (MI) and in 21 ones with macrofocal MI. Control group comprised 30 age-matched men. Diagnosis of MI was confirmed by traditional functional tests and laboratory methods. It was shown that levels of TNF-alpha and MG-PL transport complexes were elevated regardless of MI type whereas acute phase reactants increased only in patients with macrofocal MI These patients also had enhanced IL-6 and IL-8 levels with gradual normalization of the former. In microfocal IM, IL-8 increased only by day 14. Inhibitory action of TNF-alpha appears to be insufficient to suppress effect of macrofocal IM but may be responsible for its selective effect on acute phase reactants. The above differences can be used as additional criteria for differential diagnosis of micro- and macrofocal MI especially in patients with repeated MI or His bundle block when traditional ECG data are of poor informative value.
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PMID:[Cytokine and acute phase inflammation reactant levels in men with myocardial infarction]. 2013 80

Staphylococcal superantigen-like proteins (SSLs) constitute a family of exoproteins exhibiting structural similarities to superantigens and enterotoxins but no superantigenic activity. In this article, we present evidence that SSL5 specifically binds to matrix metalloproteinase 9 (MMP-9) and inhibits its enzymatic activity. When human neutrophil cell lysate was applied to recombinant His-tagged SSL5 conjugated to Sepharose, the bound fraction gave a major band of approximately 100 kDa in SDS-polyacrylamide gel electrophoresis. This protein was identified as the proform of MMP-9 (proMMP-9) by peptide mass fingerprinting analysis. The recombinant SSL5-Sepharose also bound to proMMP-9 secreted by interleukin 8 (IL-8)-stimulated neutrophils and HT1080 fibrosarcoma cells. Surface plasmon resonance analysis revealed that recombinant SSL5 bound to proMMP-9 with rather high affinity (dissociation constant [K(D)] = 1.9 nM). Recombinant SSL5 was found to effectively inhibit MMP-9-catalyzed hydrolysis of gelatin and a synthetic fluorogenic peptide in a noncompetitive manner (K(i) = 0.097 nM), as assessed by zymography and the fluorescence quenching method. Finally, the transmigration of neutrophils across Matrigel basement membranes in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was suppressed by the presence of recombinant SSL5. We discuss possible roles that SSL5 may play in immune evasion of staphylococci by inhibiting MMP and interfering with leukocyte trafficking.
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PMID:Staphylococcal superantigen-like protein 5 inhibits matrix metalloproteinase 9 from human neutrophils. 2047 83

We present here the unusual case of a male newborn infant who showed progressive severe cholestasis. The infant's gestational age was 37 weeks, and his birth weight was 2134 g. His serum level of direct bilirubin gradually increased from the 6th day of life and reached 257.5 micromol/L on the 22nd day of life. We could not find any cause for his cholestasis, but his serum level of ferritin was extremely elevated at 9211.0 ng/mL. Because we felt that his clinical condition might be related to hypercytokinemia caused by an immunologic reaction, steroid pulse therapy and cyclosporine were administered. His condition improved, and his direct bilirubin and ferritin levels declined. From the investigation of his cytokine profile, we found a preferentially elevated level of serum interleukin 17 (IL-17) (96.1 pg/mL) and high level of chemokines IL-8 and macrophage inflammatory protein 1beta. The IL-17 level gradually decreased to 7.5 pg/mL by the 124th day of life. The infant was successfully discharged from the children's hospital but later developed epilepsy at 11 months and asthma at 1 year, 2 months of age. Although we have not yet reached a definitive diagnosis, this case may be the first to show a relationship between cholestasis and an elevated serum IL-17 level in the neonatal period.
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PMID:Selectively high levels of serum interleukin 17 in a newborn infant with progressive severe cholestasis. 2054 43


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