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)

To avoid the need to use animals to test the skin irritancy potential of chemicals and cosmetics, it is important to establish an in vitro method based on the reconstructed human epidermal model. To evaluate skin irritancy efficiently and sensitively, we determined the gene expression induced by a topically-applied mild irritant sodium dodecyl sulfate (SDS) in a reconstructed human epidermal model LabCyte EPI-MODEL (LabCyte) using a DNA microarray carrying genes that were related to inflammation, immunity, stress and housekeeping. The expression and secretion of IL-1alpha in reconstructed human epidermal culture is known to be induced by irritation. We detected the induction of IL-1alpha expression and its secretion into the cell culture medium by treatment with 0.075% SDS for 18 h in LabCyte culture using DNA microarray, quantitative reverse-transcription polymerase chain reaction (RT-PCR) and ELISA. DNA microarray analysis indicated that the expression of 10 of the 205 genes carried on the DNA microarray was significantly induced in a LabCyte culture by 0.05% or 0.075% SDS irritation for 18 h. RT-PCR analysis confirmed that SDS treatment significantly induced the expressions of interleukin-1 receptor antagonist (IL-1RN), FOS-like antigen 1 (FOSL1), heat shock 70 kDa protein 1A (HSPA1) and myeloid differentiation primary response gene (88) (MYD88), as well as the known marker genes for irritation IL-1beta and IL-8 in a LabCyte culture. Our results showed that a DNA microarray is a useful tool for efficiently evaluating mild skin irritation using a reconstructed human epidermal model.
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PMID:Evaluation of the skin irritation using a DNA microarray on a reconstructed human epidermal model. 1918 76

Inflammatory bowel disease (IBD) is a chronic and recurring inflammation of the gastrointestinal tract, associated with a dysregulation of the mucosal immune system. There is an increasing prevalence of IBD; however, current pharmaceutical treatments are only moderately effective and have been associated with potential long-term toxicity. Lysozyme, a well-known antimicrobial protein found in large quantities in hen egg white, is a promising alternative for the treatment of IBD. A porcine model of dextran sodium sulfate (DSS)-induced colitis was used to examine the effect of hen egg lysozyme (HEL) supplementation on intestinal inflammation. Treatment with DSS resulted in weight loss, severe mucosal and submucosal inflammation, colonic crypt distortion, muscle wall thickening, down-regulation of mucin gene expression, and increased gastric permeability, but these symptoms were attenuated following supplementation with HEL and restored to basal levels observed in untreated control animals. Treatment with HEL also significantly reduced the local expression of pro-inflammatory cytokines TNF-alpha, IL-6, IFN-gamma, IL-8, and IL-17 while increasing the expression of the anti-inflammatory mediators IL-4 and TGF-beta, indicating that HEL may function as a potent anti-inflammatory and immunomodulator. Furthermore, the concomitant increases in TGF-beta and Foxp3 levels suggest that HEL may aid in restoring gut homeostasis by activating regulatory T cells, which are important in the regulation of the mucosal immune system. These results suggest that HEL is a promising novel therapeutic for the treatment of IBD.
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PMID:Hen egg lysozyme attenuates inflammation and modulates local gene expression in a porcine model of dextran sodium sulfate (DSS)-induced colitis. 1923 58

Effects of dietary taurine on the experimental colitis induced by dextran sulfate sodium (DSS) were studied. C57BL/6 mice administrated taurine or placebo for 5 days were given 3% DSS to induce acute. The colitis was as-sessed using indices such as diarrhea/bleeding scores, colon length change, histological score and tissue myeloperoxidase (MPO) activity. Further, tissue mRNA levels of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2, were determined by real-time PCR. Taurine supplementation significantly attenuated the severity of diarrhea, colon shortening, histological score, MPO activity elevation and abnormal MIP-2 gene expression, indicating that taurine prevents DSS-induced colitis. Taurine also inhibited the TNF-alpha-induced secretion of IL-8 (a human homologue of MIP-2) from human intestinal epithelial Caco-2 cells. Inhibition of chemokine secretion from intestinal cells may be involved in the mechanisms underlying the cytoprotective function of taurine in the intestinal epithelium.
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PMID:Dietary taurine attenuates dextran sulfate sodium (DSS)-induced experimental colitis in mice. 1923 57

The chemokine IL-8 is critically important in inflammatory processes in human tissues, and IL-8 interactions with sulfated glycosaminoglycans have been implicated in modification of inflammatory responses in bronchial epithelium. To determine the role of chondroitin-4-sulfate (C4S) in mediating effects of IL-8, we silenced the enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B [ASB]) that removes the 4-sulfate group from C4S, in the IB3-1 and C38 bronchial epithelial cell lines and in normal primary bronchial epithelial cells. When ASB was silenced and IL-8 production stimulated by exposure to TNF-alpha, ASB activity declined by roughly 75%, cellular C4S content increased by over 7.5 microg/mg protein, cell-bound IL-8 increased by over 530 pg/mg protein, and secreted IL-8 declined by over 520 pg/mg protein in all cell lines (P < 0.001). When cell lysates were immunoprecipitated with C4S antibody after ASB silencing and TNF-alpha, the IL-8 content of the immunoprecipitate was approximately 500 pg/mg protein, indicating that most of the cell-bound IL-8 was associated with C4S. Cell fractionation demonstrated that the IL-8 content associated with the cell membranes was about twice that of the cytosolic fraction. Also, ASB appeared to localize in the cell membrane, as well as in lysosomes. Neutrophil attraction to the cell lysates increased after ASB silencing, consistent with increased attraction to the cell-bound IL-8. These findings provide evidence for the influential role of ASB and C4S in the regulation of IL-8 secretion, and suggest that changes in ASB activity and C4S content may have a significant impact on IL-8-mediated inflammatory responses.
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PMID:Cell-bound IL-8 increases in bronchial epithelial cells after arylsulfatase B silencing due to sequestration with chondroitin-4-sulfate. 1934 17

Conventional therapies for the treatment of inflammatory bowel disease (IBD) have demonstrated limited efficacy and potential toxicity; therefore, there is a need for novel therapies that can safely and effectively treat IBD. Recent evidence has indicated that amino acids may play a role in maintaining gut health. L-tryptophan has been shown to reduce oxidative stress and improve neurological states. The objective of this study was to assess the therapeutic effects of L-tryptophan in a porcine model of dextran sodium sulfate (DSS)-induced colitis. DSS was administered to piglets via intragastric catheter for 5 days followed by tryptophan administration at 80% of the daily recommended intake. The severity of colitis was assessed macroscopically and histopathologically, and intestinal permeability was monitored in vivo by D-mannitol analysis. The effect of tryptophan on the local expression of key mediators of inflammation and IBD pathogenesis was examined at the protein and gene expression levels. Supplementation with tryptophan ameliorated clinical symptoms and improved weight gain to feed intake conversion ratios. Histological scores and measurements were also improved, and gut permeability was notably reduced in tryptophan-supplemented animals. Moreover, tryptophan reduced the expression of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, interferon (IFN)-gamma, IL-12p40, IL-1beta and IL-17, as well as IL-8 and intracellular adhesion molecule-1, and resulted in increased expression of apoptosis initiators caspase-8 and Bax. These results demonstrate that L-tryptophan supplementation can reduce inflammation and enhance the rate of recovery in DSS-induced colitis and may be an effective immunomodulating agent for the treatment of IBD.
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PMID:l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis. 1942 34

The effects of lactobacilli on impaired intestinal barrier function and paracellular permeability were evaluated in human epithelial Caco-2 cells treated with tumor necrosis factor-alpha and in mice with colitis induced by dextran sodium sulfate (DSS). Filter-grown Caco-2 monolayers were used as the intestinal epithelial model. Among the 4 lactobacilli studied, Lactobacillus rhamnosus OLL2838 most effectively suppressed barrier impairment and increased IL-8 secretion induced by tumor necrosis factor-alpha in Caco-2 cells; however, the conditioned medium from OLL2838 did not show any effect on barrier functions. The in vivo effects of OLL2838 on intestinal epithelial barrier function and colonic inflammation were assessed in DSS-induced colitis of BALB/c mice. Oral treatment with both live and heat-killed OLL2838 suppressed weight loss and recovered colon length. Additionally, barrier function was restored by the administration of live and heat-killed OLL2838 to the DSS-treated animals, which conferred protection against the increase in mucosal permeability associated with DSS-induced colitis. This may at least partially be because of the increased expression of zonula occludens-1 (4.8-fold) and myosin light-chain kinase (3.1-fold) in intestinal epithelial cells isolated from mice of the heat-killed OLL2838 group. Therefore, L. rhamnosus OLL2838 would be useful in the treatment of gastrointestinal diseases such as inflammatory bowel disease.
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PMID:Lactobacillus rhamnosus alleviates intestinal barrier dysfunction in part by increasing expression of zonula occludens-1 and myosin light-chain kinase in vivo. 1944 72

The polyphenols in fruits and vegetables may be partly responsible for the health-promoting effects attributed to fruit and vegetable intake. Although their properties have been relatively well studied, the activity of their metabolites, produced after ingestion, has been poorly investigated. Thus, the aim of this work was to study the potential anti-inflammatory effect of 18 polyphenol metabolites, derived from colon microbiota. They were screened by measuring prostaglandin E(2) (PGE(2)) production by CCD-18 colon fibroblast cells stimulated with IL-1beta. Metabolites that inhibited more than 50% PGE(2) production were hydrocaffeic (HCAF), dihydroxyphenyl acetic (dOHPA), and hydroferulic acid (HFER), that subsequently were tested with the writhing and paw pressure test in rodents where all three compounds showed an anti-inflammatory effect. The effect of HCAF administered orally (50 mg/kg) was also tested in the dextran sodium sulfate (DSS)-induced colitis model. Weight loss and fecal water content were more pronounced in DSS rats than in DSS-HCAF treated rats. HCAF treatment diminished the expression of the cytokines IL-1beta, IL-8, and TNF-alpha, reduced malonyldialdehyde (MDA) levels and oxidative DNA damage (measured as 8-oxo-2'-deoxyguanosine levels) in distal colon mucosa. These results indicate that HCAF, dOHPA, and HFER have anti-inflammatory activity in vitro and in vivo.
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PMID:Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models. 1955 20

Interaction between chemokines and heparan sulfate (HS) is essential for leukocyte recruitment during inflammation. Previous studies have shown that a non-HS-binding mutant form of the inflammatory chemokine CCL7 can block inflammation produced by wild-type chemokines. This study examined the anti-inflammatory mechanism of a non-HS-binding mutant of the homeostatic chemokine CXCL12. Initial experiments demonstrated that mutant CXCL12 was an effective CXCR4 agonist. However, this mutant chemokine failed to promote transendothelial migration in vitro and inhibited the haptotactic response to wild-type CCL7, CXCL12, and CXCL8, and naturally occurring chemoattractants in synovial fluid from the rheumatoid synovium, including CCL2, CCL7, and CXCL8. Notably, intravenous administration of mutant CXCL12 also inhibited the recruitment of leukocytes to murine air pouches filled with wild-type CXCL12. Following intravenous administration, wild-type CXCL12 was cleared from the circulation rapidly, while the mutant chemokine persisted for >24 h. Chronic exposure to mutant CXCL12 in the circulation reduced leukocyte-surface expression of CXCR4, reduced the chemotactic response of these cells to CXCL12, and inhibited normal chemokine-mediated induction of adhesion between the alpha4beta1 integrin, VLA-4, and VCAM-1. These data demonstrate that systemic administration of non-HS-binding variants of CXCL12 can mediate a powerful anti-inflammatory effect through chemokine receptor desensitization.
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PMID:Anti-inflammatory therapy by intravenous delivery of non-heparan sulfate-binding CXCL12. 1966 20

Patients with rheumatoid arthritis often conduct bathing in hot mineral water with a high concentrations of sulfate compounds in the water and ambient air. We investigated the effect of hyperthermia and sulfur as possible stress factors at transcriptional level in several proinflammatory genes in fibroblast like synoviocytes. We mimicked the classical balneological treatment. Cells were exposed to 30 minutes of hyperthermia (41-42 degrees C) or sulfur (2 mM NaHS). Indeed, both factors were acting as stressors, inducing a profound expression of heat shock protein 70 (HSP70). Stimulation of the cells with IL1beta induced a series of proinflammatory genes (IL1alpha, IL1beta, TNFalpha, IL8, monocyte chemoattractant peptide-1 and COX-2), but if the cells were treated with hyperthermia prior to IL1beta expression, gene expressions were significantly decreased up to 8 h. Treatment with sulfur alone induced expression of observed genes up to 12 h. We may conclude that hyperthermia as a balneological mean has indeed a protective effect on cells, but sulfur, which at first we considered as an antiinflammatory mean, had actually an opposite effect and induced expression of proinflammatory genes. Our data confirmed that the effect of hyperthermia as balneological mean treatment is beneficial, but sulfur treatment must be taken in reconsideration.
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PMID:Beneficial effects of cellular stress response in traditional spa treatment of rheumatoid arthritis. 1972 58

Probiotics have been used to treat human gastrointestinal inflammations including inflammatory bowel disease (IBD). However, the exact mechanisms by which probiotics act to protect against intestinal inflammation have yet to be fully elucidated. The aim of this study was to evaluate anti-inflammatory effects of Lactococcus lactis subsp. cremoris FC using in vivo and in vitro inflammation models. Colitis was induced in C57BL/6 mice by administration of 3% dextran sulfate sodium to drinking water. In the cellular level assessment, a gut inflammation model with the co-culture system consisting Caco-2 cells and RAW264.7 cells stimulated by LPS was used. Administration of L. lactis subsp. cremoris FC significantly ameliorated shortening of colon length and histological score of the colon in DSS-induce colitis mice. In addition, the treatment of L. lactis subsp. cremoris FC improved the aberrant mRNA expression in inflamed tissue near to control level through notable suppression of TNF-alpha (P<0.05), IFN-gamma (P<0.05), IL-6, iNOS, and MIP-2 mRNA expression. In addition, in a gut inflammation model, treatment with L. lactis subsp. cremoris FC resulted in significant down-regulation of IL-8 mRNA expression in Caco-2 cells and inhibition of NF-kappaB nuclear translocation in RAW264.7 cells. Our findings indicate that administration of L. lactis subsp. cremoris FC improves negative effects of DSS-induced colitis in mice through the inhibition of inflammatory cell infiltration.
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PMID:Lactococcus lactis subsp. cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice. 1973 97


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