UNIPROT:P10145 - FACTA Search

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)

Ambient particulate matter (PM) has been shown to be associated with mortality and morbidity. Diesel exhaust particles (DEP) contribute to ambient PM. Alveolar macrophages (AM) are important targets for PM effects in the lung. The effects of DEP exposure on human AM response to lipopolysachharide (LPS; from gram-negative bacteria) challenge in vitro were determined by monitoring the production of interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)). The roles of organic compounds and carbonaceous core of DEP in response to LPS were evaluated by comparing the DEPs effect to that of carbon black (CB), a carbonaceous particle with few adsorbed organic compounds. AMs were exposed in vitro to Standard Reference Material (SRM) DEP 2975, SRM DEP 1650, SRM 1975 (a dichloromethane extract of SRM DEP 2975) and CB particles for 24 h. DEPs induced a decreased secretion of IL-8, TNF-alpha and PGE(2) in response to a subsequent LPS stimulation. DEPs also show suppressive effect on the release of inflammatory mediators when stimulated with lipoteichoic acid, a product of gram positive bacteria. In summary, in vitro exposure of human AM to DEPs significantly suppress AM responsiveness to gram-negative and positive bacterial products, which may be a contributing factor to the impairment of pulmonary defense.
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PMID:Effects of diesel exhaust particles on human alveolar macrophage ability to secrete inflammatory mediators in response to lipopolysaccharide. 1636 Mar

Essential fatty acids are not only energy-rich molecules; they are also an important component of the membrane bilayer and recently have been implicated in induction of fatty acid synthase and other genes. Using gene chip analysis, we have found that arachidonic acid, an omega-6 fatty acid, induced 11 genes that are regulated by nuclear factor-kappaB (NF-kappaB). We verified gene induction by omega-6 fatty acid, including COX-2, IkappaBalpha, NF-kappaB, GM-CSF, IL-1beta, CXCL-1, TNF-alpha, IL-6, LTA, IL-8, PPARgamma, and ICAM-1, using quantitative reverse transcription-PCR. Prostaglandin E(2) (PGE(2)) synthesis was increased within 5 minutes of addition of arachidonic acid. Analysis of upstream signal transduction showed that within 5 minutes of fatty acid addition, phosphatidylinositol 3-kinase (PI3K) was significantly activated followed by activation of Akt at 30 minutes. Extracellular signal-regulated kinase 1 and 2, p38 and stress-activated protein kinase/c-Jun-NH(2)-kinase were not phosphorylated after omega-6 fatty acid addition. Thirty minutes after fatty acid addition, we found a significant 3-fold increase in translocation of NF-kappaB transcription factor to the nucleus. Addition of a nonsteroidal anti-inflammatory drug (NSAID) caused a decrease in COX-2 protein synthesis, PGE(2) synthesis, as well as inhibition of PI3K activation. We have previously shown that NSAIDs cause an inhibition of arachidonic acid-induced proliferation; here, we have shown that arachidonic acid-induced proliferation is also blocked (P < 0.001) by PI3K inhibitor LY294002. LY294002 also significantly inhibited the arachidonic acid-induced gene expression of COX-2, IL-1beta, GM-CSF, and ICAM1. Taken together, the data suggest that arachidonic acid via conversion to PGE(2) plays an important role in stimulation of growth-related genes and proliferation via PI3K signaling and NF-kappaB translocation to the nucleus.
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PMID:Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer. 1645 98

The roots of Platycodon grandiflorum, which belongs to the Campanulaceae family, have been used as a food material and as a traditional Oriental medicine. The effect of P. grandiflorum against lipopolysaccharide (LPS)-stimulated inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, reverse transcription-polymerase chain reaction, prostaglandin E(2 )(PGE(2)) immunoassay, nitric oxide (NO) detection assay, and interleurkin-8 (IL- 8) immunoassay on BV2 microglial cells. The aqueous extract of P. grandiflorum was shown to suppress PGE(2 )synthesis and NO production by inhibiting LPS-stimulated cyclooxygenase (COX)-2 activity and expression of inducible NO synthase (iNOS) mRNAs. In addition, the treatment with P. grandiflorum reduced the LPS-induced IL-8 release. These results suggest that P. grandiflorum inhibits PGE(2) and NO production through its suppression of LPS-induced COX-2 and iNOS expression, and also reduces IL-8 secretion by microglial cells.
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PMID:Effects of Platycodon grandiflorum on lipopolysaccharide-stimulated production of prostaglandin E2, nitric oxide, and interleukin-8 in mouse microglial BV2 cells. 1682 1

We have investigated the hypothesis that the expression of the enzymes involved in PGE(2) synthesis in the human uterus is co-ordinated. We have studied (i) the mRNA expression of the enzymes involved in PGE(2) synthesis [phospholipases (cPLA(2) and sPLA(2)), prostaglandin H synthase (PGHS)-2 and PG E synthases (PGES-1 and -2)] and their relationship to the expression of inflammatory cytokines in samples of myometrium obtained from pregnant women undergoing caesarean section (LSCS) either before or after the onset of labour at or before term; and (ii) the effect of IL-1beta, IL-6, TNF-alpha, PGE(2) and stretch on PGE(2) enzyme mRNA expression. We found that cPLA(2), sPLA(2) and PGHS-2 mRNA expression were greater in labour samples; cPLA(2), sPLA(2), PGHS-2, PGES-1 and -2 mRNA expression were greater in lower- than upper-segment samples; and there was no effect of gestational age. PGHS-2 mRNA levels correlated with those of PGES-1, cPLA(2), IL-1beta and IL-8; PGES-1 mRNA levels correlated with those of IL-1beta, IL-8 and cPLA(2). In primary cultures of uterine myocytes, cPLA(2) mRNA expression was increased by IL-1beta and IL-6; PGHS-2 mRNA expression was increased by IL-1beta, PGE(2) and stretch; and PGES-1 mRNA expression was increased by IL-1beta only. These data show that labour is associated with increased expression of the enzymes involved in PGE(2) synthesis and their expression is greater in the lower uterine segment. The presence of associations between the levels of PGE(2) enzyme mRNA expression and the effects of IL-1beta suggest that their expression is co-ordinated and that IL-1beta is the responsible factor.
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PMID:Myometrial prostaglandin E2 synthetic enzyme mRNA expression: spatial and temporal variations with pregnancy and labour. 1693 97

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface molecule that is expressed by neutrophils and monocytes. TREM-1 expression is modulated by various ligands for TLRs in vitro and in vivo. However, the influence of PGE(2), a potential mediator of inflammation, on TREM-1 expression has not been elucidated. In this study, we examined the effects of PGE(2) on LPS-induced TREM-1 expression by resident murine peritoneal macrophages (RPM) and human PBMC. PGE(2) significantly induced murine TREM-1 (mTREM-1) expression by RPM. Up-regulation of TREM-1 expression was specific to PGE(2) among arachidonic acid metabolites, while ligands for chemoattractant receptor-homologous molecule expressed on Th2 cells and the thomboxane-like prostanoid receptor failed to induce mTREM-1 expression. PGE(2) also increased expression of the soluble form of TREM-1 by PBMC. LPS-induced TREM-1 expression was regulated by endogenous PGE(2) especially in late phase (>2 h after stimulation), because cyclooxygenase-1 and -2 inhibitors abolished this effect at that points. A synthetic EP4 agonist and 8-Br-cAMP also enhanced mTREM-1 expression by RPM. Furthermore, protein kinase A, PI3K, and p38 MAPK inhibitors prevented PGE(2)-induced mTREM-1 expression by RPM. Activation of TREM-1 expressed on PGE(2)-pretreated PBMC by an agonistic TREM-1 mAb significantly enhanced the production of IL-8 and TNF-alpha. These findings indicate that LPS-induced TREM-1 expression on macrophages is mediated, at least partly, by endogenous PGE(2) followed by EP4 and cAMP, protein kinase A, p38 MAPK, and PI3K-mediated signaling. Regulation of TREM-1 and the soluble form of TREM-1 expression by PGE(2) may modulate the inflammatory response to microbial pathogens.
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PMID:Lipopolysaccharide-induced up-regulation of triggering receptor expressed on myeloid cells-1 expression on macrophages is regulated by endogenous prostaglandin E2. 1720 78

Periodontitis is a chronic inflammatory disease that affects the tooth supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and participate actively in the host inflammatory response to periodontopathogens, which is known to mediate local tissue destruction in periodontitis. The aim of this study was to investigate the effect of a proanthocyanidin-enriched cranberry fraction, prepared from cranberry juice concentrate, on inflammatory mediator production by gingival fibroblasts stimulated by the lipopolysaccharide (LPS) of Aggregatibacter actinomycetemcomitans. Interleukin (IL)-6, IL-8, and prostaglandin E(2) (PGE(2)) production by fibroblasts treated with the cranberry fraction and stimulated by A. actinomycetemcomitans LPS was evaluated by enzyme-linked immunosorbent assay. Changes induced by A. actinomycetemcomitans LPS and the cranberry fraction in the expression and phosphorylation state of fibroblast intracellular signaling proteins were characterized by antibody microarrays. The LPS-induced IL-6, IL-8, and PGE(2) responses of gingival fibroblasts were inhibited by treatment with the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. Cranberry components also reduced cyclooxygenase 2 expression. This study suggests that cranberry juice contains molecules with interesting properties for the development of new host-modulating therapeutic strategies in the adjunctive treatment of periodontitis.
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PMID:Cranberry components inhibit interleukin-6, interleukin-8, and prostaglandin E production by lipopolysaccharide-activated gingival fibroblasts. 1730 18

Conjugated linoleic acids (CLA), derivatives of linoleic acid found in food products, inhibit chemically induced skin cancers in mice. However, their potential photoprotective properties remain unexplored. We examined whether CLA may modulate ultraviolet radiation (UVR)-induced secretion of interleukin (IL)-8 and prostaglandin E2 (PGE(2)), mediators implicated in UVR-induced inflammation and carcinogenesis, in human skin cells. Since tumour necrosis factor (TNF)-alpha is an early mediator of UVR effects, we also examined influence of CLA on TNF-alpha-induced mediator release. HaCaT keratinocytes were supplemented with CLA isomers cis-9-trans-11 (c9,t11-CLA; > or =90%), trans-10-cis-12 (t10,c12-CLA; > or =90%) or all trans-trans isomers (tt-CLA; 23.7%) in tetrahydrofuran/fetal calf serum (THF/FCS) or THF/FCS control. Supplementation of keratinocytes with c9,t11-CLA reduced Ultraviolet B(UVB)-induced IL-8 from 37 113 +/- 2903 pg/ng protein in control cells to 14 167 +/- 2063 pg/ng protein (P < 0.001). Similarly, t10,c12-CLA reduced UVB-induced IL-8 to 9786 +/- 1291.5 pg/ng protein (P < 0.001). Additionally, t10,c12-CLA and tt-CLA inhibited TNF-alpha-induced IL-8 from 11 669 +/- 1692 pg/ng protein in control cells to 5540 +/- 191 (P < 0.001) and 8082 +/- 1298 pg/ng (P < 0.01) protein, respectively. UVB-induced PGE(2) release was reduced by tt-CLA supplementation, from 4.8 +/- 1.2 to 1.6 +/- 0.8 pg/mg protein (P < 0.01), but increased by t10,c12-CLA to 8.8 +/- 1 pg/mg protein (P < 0.001). Influence of CLA on UVB-induced PGE(2) release was further explored in CCD922SK dermal fibroblasts. CLA isomers reduced UVB-induced PGE(2) in fibroblasts, reaching significance with c9,t11-CLA (98 +/- 5 falling to 0 pg/mg protein, P < 0.05). Hence, CLA isomers differentially modulate UVB effects on skin cells in vitro. CLA-containing foods have potential in photoprotection; the cutaneous effects of individual isomers warrant clinical study.
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PMID:Conjugated linoleic acids modulate UVR-induced IL-8 and PGE2 in human skin cells: potential of CLA isomers in nutritional photoprotection. 1738 16

The role of pro-inflammatory cytokines and prostaglandins in human labour is well established. Many of the mRNAs stabilised by the MAPK pathway encode inflammatory mediators, suggesting that this kinase pathway plays a major role in the regulation of inflammation. The aim of this study was to determine if the MAPK pathway regulates the inflammatory response in human gestational tissues. Placenta and fetal membranes (n=5) obtained from pregnant women undergoing Caesarean section before the onset of labour were exposed to LPS, and co-incubated in the absence or presence of 12.5, 25 and 50 microM U0126 (ERK 1/2 inhibitor), SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor). After 18 h incubation, tissues were collected and ERK 1/2, p38 MAPK, and JNK total and phosphorylated protein expression was assessed by ELISA and/or Western blotting. The incubation medium was collected and TNF-alpha, IL-1beta, IL-6, IL-8, PGE(2) and PGF(2alpha) release was quantified by ELISA. Treatment of placenta and fetal membranes with LPS activated all three MAPK proteins. Co-incubation with U0126, SP600125 and SB202190 significantly suppressed LPS-stimulated activation of ERK 1/2, JNK, and p38 MAPK, respectively. All cytokine and prostaglandin release was significantly suppressed by all concentrations of U0126. LPS-stimulated IL-6, TNF-alpha, PGE(2) and PGF(2alpha) release was significantly suppressed by treatment with all concentrations of SB202190, whereas ILS-stimulated IL-1beta release was only significantly inhibited in the presence of 50 microM SB202190 and there was no effect of SB202190 on LPS-stimulated IL-8 release. SP600125 significantly repressed LPS-stimulated release of IL-1beta and TNF-alpha at all concentrations, whereas LPS-stimulated IL-6, PGE(2) and PGF(2alpha) release were inhibited at 25 and 50 microM. In conclusion, the MAPK inhibitors used in this study demonstrated differential activity against a range of sequelae commonly associated with inflammation, supporting the therapeutic potential of MAPK inhibitors in pregnancy complications associated with an aberrant inflammatory response.
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PMID:Mitogen-activated protein kinase proteins regulate LPS-stimulated release of pro-inflammatory cytokines and prostaglandins from human gestational tissues. 1743 32

Epigallocatechin-3-gallate (EGCG) is the major polyphenol component of green tea and is primarily responsible for the green tea effect. EGCG possesses two triphenolic groups in its structure. These groups are reported to be important with respect to anticarcinogenic and antioxidant effects. However, the anti-inflammatory effect of EGCG on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of EGCG in attenuating the inflammatory response induced by interleukin (IL)-1beta+beta-amyloid (25-35) fragment (Abeta) in human astrocytoma, U373MG cells. EGCG significantly inhibited the IL-1beta+Abeta (25-35)-induced IL-6, IL-8, vascular endothelial growth factor (VEGF) and prostaglandin (PG)E(2) production at 24 h (P<.01). The maximal inhibition rate of IL-6, IL-8, VEGF and PGE(2) production by EGCG was approximately 54.40%, 56.01%, 69.06% and 47.03%, respectively. EGCG also attenuated the expression of cyclooxygenase-2 and activation of nuclear factor-kappaB induced by IL-1beta+Abeta (25-35). We demonstrated that EGCG suppresses IL-1beta+Abeta (25-35)-induced phosphorylation of the mitogen-activated protein kinase p38 and the c-Jun N-terminal kinase. In addition, EGCG induced the expression of mitogen-activated protein kinase phosphatase-1. These results provide new insight into the pharmacological actions of EGCG and its potential therapeutic application to various neurodegenerative diseases such as AD.
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PMID:Epigallocatechin-3-gallate suppresses NF-kappaB activation and phosphorylation of p38 MAPK and JNK in human astrocytoma U373MG cells. 1744 59

Proinflammatory prostaglandins and cytokines are involved in the initiation of human labor and delivery. Although cyclopentenone prostaglandins regulate the formation of these prolabor mediators via nuclear factor-kappaB (NF-kappaB) and/or peroxisome proliferator-activated receptor-gamma, recent evidence suggests that they do not exist in vivo. Cyclopentenone isoprostanes (IsoPs), which are highly reactive structural isomers of bioactive cyclopentenone prostaglandins, do exist physiologically and have been shown to inhibit the inflammatory response in macrophages. Therefore the aim of this study was to determine the effect of the synthetic cyclopentenone IosP 15-A(2)-IsoP on the expression of prolabor mediators in human gestational tissues. Human placenta and gestational membranes (n=5) were incubated in the absence or presence of 12.5, 25, and 50 microM 15-A(2)-IsoP with 10 microg/ml lipopolysaccharide (LPS). Treatment of placenta and fetal membranes with 15-A(2)-IsoP caused a dose-dependent decrease in LPS-stimulated release of the cytokines IL-1beta, IL-6, IL-8, and TNF-alpha and the prostaglandins PGE(2) and PGF(2)alpha. NF-kappaB p65 DNA binding activity was significantly inhibited by treatment with 50 microM 15-A(2)-IsoP. Collectively, these data suggest that 15-A(2)-IsoP exhibits antiinflammatory properties via antagonism of NF-kappaB activity. Cyclopentenone IsoPs may serve as negative feedback regulators of the inflammatory response in human gestational tissues.
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PMID:Antiinflammatory effects of the cyclopentenone isoprostane 15-A(2)-IsoP in human gestational tissues. 1751 58

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