Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to characterize the pattern of cytokine gene expression by human corneal epithelial cells (HCEC) in response to interleukin-1 (IL-1). Primary cultured HCEC (P-HCEC) or SV40 transformed HCEC (SV40-HCEC) were treated for 6 hr with serum-free growth-media alone or with recombinant human IL-1beta or IL-1alpha (10 ng ml(-1)). 33P labeled cDNA was generated from total RNA, then hybridized to a human cytokine expression array. An autoradiograph was generated for each experimental condition and results analysed semi-quantitatively. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect mRNA for IL-8, growth related oncogene-beta (GRO-beta), intercellular adhesion molecule (ICAM)-1 and Ephrin A5. P-HCEC and SV40-HCEC demonstrated comparable cytokine profiles. For P-HCEC (n=2) the expression of 35 genes was upregulated or only detectable following IL-1beta treatment whereas the expression of nine genes was downregulated or undetectable after IL-1beta treatment. In SV40-HCEC (n=3), the expression of 48 genes was upregulated or only detectable following IL-1beta treatment and the expression of 10 genes was downregulated or undetectable after IL-1beta treatment. Some genes that demonstrated increased expression included cadherin-5, ICAM-1, GRO-alpha, GRO-beta, GRO-gamma, Activin A (bA subunit), tumor necrosis factor-alpha, IL-6, and IL-8. Genes that showed decreased expression included the chemokine receptor-CXCR-4, ciliary neurotrophic factor (CNTF), c-kit ligand, Ephrin A5, G-protein coupled receptor RDC-1 and FGF family FGFR2. Bayesian analysis of the SV40-HCEC data (n=3) revealed the expression of 15 genes that were significantly (p<0.05) differentially regulated. Within these 15 genes, the expression of chemokines (GRO-alpha, GRO-beta, IL-8), fibroblast growth factor 13 and the cytokine IL-6 were the most upregulated, while ephrin A5 and chemokine receptor-4 were the most downregulated. IL-1alpha treatment (n=1 P-HCEC; n=1 SV40-HCEC) produced results very similar to IL-1beta treatment. RT-PCR revealed differential regulation of IL-8, GRO-beta, ICAM-1 and ephrin A5 in accordance with gene array data. In conclusion, the data demonstrate that IL-1 treatment of HCEC differentially regulates the expression of other cytokine and related genes, thus adding to the body of evidence that IL-1 is a major mediator of ocular surface inflammatory reactions. Since the expression of a large number of genes can be studied simultaneously, gene array studies such as these offers the advantage of understanding global changes in response to a specific stimulus. Thus our study provides insight in to the ocular surface response in conditions of inflammation and corneal wound healing where the levels of IL-1 are known to be increased.
...
PMID:The effect of interleukin-1 on cytokine gene expression by human corneal epithelial cells. 1567 Jul 96

Food poisoning due to staphylococcal enterotoxins (SEs) affects hundreds of thousands of people each year. Little is known about how SEs initiate immune responses and cause pathogenesis. Here, we demonstrate that cultured human intestinal myofibroblasts (IMFs) bind SEs in an MHC class II-dependent fashion. IMFs respond to SE exposure with increased secretion of IL-6, IL-8, and TNF-alpha. A significant proliferative T cell response was observed when MHC class II-expressing IMFs were pulsed with SEA and cocultured with human CD4(+) T cells. In conclusion, our findings support the hypothesis that IMFs may play an important role in pathology associated with staphlococcocal enterotoxigenic disease.
...
PMID:Class II MHC-expressing myofibroblasts play a role in the immunopathogenesis associated with staphylococcal enterotoxins. 1568 69

Recent data have indicated that CRP (C-reactive protein) plays a role in atherosclerosis, in addition to being a marker for inflammatory diseases. IL-8 (interleukin-8), a CXC chemokine, is present in human coronary atheroma and promotes monocyte-endothelial cell adhesion. In the present study, we examined the effect of pitavastatin (NK-104), a synthetic statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitor), on IL-8 production induced by CRP in human AoEC (aortic endothelial cells). We also investigated whether CRP can induce IL-8 production and if the activation of signalling pathways are functionally related. The concentrations of IL-8 in the media after stimulation with CRP were measured by ELISA, and the expression of IL-8 mRNA was assessed by Northern blot. The phosphorylation of MAPKs (mitogen-activated protein kinases) was determined by Western blot. The production of IL-8 induced by CRP (10 microg/ml) was enhanced significantly and was inhibited by pitavastatin. The expression of IL-8 mRNA was increased in a dose-dependent manner after stimulation with CRP (1-100 microg/ml), whereas expression of IL-8 mRNA induced by CRP (50 microg/ml) was significantly diminished by 5 microM pitavastatin. Furthermore, specific MAPK inhibitors (PD98059, SB203580 and SP600125) inhibited the expression of IL-8 mRNA induced by CRP (50 microg/ml). The phosphorylation of all three MAPKs [ERK (extracellular-signal-regulated kinase), p38 MAPK and JNK (c-Jun N-terminal kinase)] induced by CRP (10 microg/ml) was also significantly inhibited by pitavastatin. Our results suggest that CRP may play a role in atherosclerosis via IL-8 production and pitavastatin may prevent the progression of atherosclerosis not only by lowering plasma low-density lipoprotein cholesterol levels, but also by suppressing IL-8 production in endothelial cells through the inhibition of MAPK (ERK, p38 MAPK and JNK) pathways.
...
PMID:Inhibitory effect of pitavastatin (NK-104) on the C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells. 1570 Oct 58

Serum amyloid A (SAA) is an acute-phase protein whose levels positively correlate with disease activity in inflammatory bowel diseases. In this study we investigated the impact of SAA on NF-kappaB signaling and proinflammatory gene expression in intestinal epithelial cells (IEC). Human HT-29 and Caco-2 monolayers were stimulated with recombinant SAA and NF-kappaB activation/NF-kappaB-dependent gene expression measured. Adenoviral dominant negative mutants IkappaB-alpha (Ad5IkappaBAA) were utilized to determine the contribution of NF-kappaB signaling pathway to SAA-dependent gene expression. Intestinal explant and primary IEC derived from kappaB-EGFP transgenic mice were exposed to SAA and NF-kappaB-dependent enhanced green fluorescent protein (EGFP) fluorescence measured. SAA induced IkappaB-alpha degradation, RelA serine 536 (S536) phosphorylation, NF-kappaB transcriptional activity, RelA recruitment to the IL-8 gene promoter and endogenous gene expression (IL-8, COX-2) in HT-29 cells. Further, Ad5IkappaBAA abrogated SAA-induced RelA nuclear translocation, NF-kappaB transcriptional activity and IL-8 gene expression. SAA-dependent IL-8 gene expression required activation of the MAPK ERK, p38 and JNK in HT-29 cells. Finally, SAA induced EGFP expression in intestinal explants isolated from kappaB-EGFP transgenic mice and enhanced RelA and IkappaBalpha phosphorylation in primary IEC. This indicates that SAA potentially participate in the inflammatory process by virtue of its ability to activate proinflammatory signaling in IEC.
...
PMID:Serum amyloid A activates NF-kappaB and proinflammatory gene expression in human and murine intestinal epithelial cells. 1572 47

Infection and uterine stretch are the common causes of preterm labor. IL-1beta plays a key role in infection-induced preterm labor and increases prostaglandin H synthase 2 (PGHS-2) and IL-8 expression. We have shown that mechanical stretch of uterine myocytes in vitro up-regulates the expression of PGHS-2 and IL-8. In this study, we tested the hypotheses that both IL-1beta and mechanical stretch increase the myometrial expression of PGHS-2 and IL-8 via MAPK activation and that their effects are synergistic. MAPK activation was assessed in myocytes obtained from pregnant women undergoing cesarean section before the onset of labor after exposure to IL-1beta and stretch either alone or in combination. Specific inhibitors of ERK, p38, and c-Jun N-terminal kinase were used to define the role of each in the increased expression of PGHS-2 and IL-8 mRNA. We found that both IL-1beta and stretch activated all three MAPK subtypes but that they had no synergistic effect. The inhibitor studies showed that stretch-induced increases in both PGHS-2 and IL-8 mRNA expression were ERK1/2 and p38 dependent and that IL-1beta-induced increases of PGHS-2 mRNA expression were also ERK1/2 and p38 dependent, but those of IL-8 were dependent only on ERK1/2 activation. These data show that exposure of human uterine myocytes to both stretch and IL-1beta activates the MAPK system, which is responsible for the increase in PGHS-2 and IL-8 mRNA expression. We found no evidence of a synergistic effect of IL-1beta and stretch on myometrial expression of PGHS-2 and IL-8 mRNA.
...
PMID:The mitogen-activated protein kinase dependent expression of prostaglandin H synthase-2 and interleukin-8 messenger ribonucleic acid by myometrial cells: the differential effect of stretch and interleukin-1{beta}. 1578 17

Campylobacter jejuni is the leading cause of food-borne illness in the USA and one of the most common causes of diarrhoea worldwide. Central to its pathogenicity is its ability to induce the production of proinflammatory cytokines such as interleukin (IL)-8 in intestinal epithelial cells. Here, we demonstrated that C. jejuni infection of intestinal epithelial cells results in the activation of the ERK and p38 mitogen-activated protein kinases and that the ERK kinase pathway is essential for IL-8 production. We found that MAP kinase stimulation leading to IL-8 secretion requires C. jejuni gene products whose production is stimulated upon contact with epithelial cells. We also found that C. jejuni flagellin is a very poor stimulator of Toll-like receptor (TLR)-5 and therefore does not play a significant role in the stimulation of cytokine production.
...
PMID:Signal transduction in Campylobacter jejuni-induced cytokine production. 1583 95

Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhalational anthrax because they initiate germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign particles and migrate to lymph nodes. However, the participation of DCs in phagocytosis and dissemination of spores has not been investigated previously. We found that human DCs readily engulfed fully pathogenic Ames and attenuated B. anthracis spores predominately by coiling phagocytosis. Spores provoked a loss of tissue-retaining chemokine receptors (CCR2, CCR5) with a concurrent increase in lymph node homing receptors (CCR7, CD11c) on the membrane of DCs. After spore infection, immature DCs displayed a mature phenotype (CD83(bright), HLA-DR(bright), CD80(bright), CD86(bright), CD40(bright)) and enhanced costimulatory activity. Surprisingly, spores activated the MAPK cascade (ERK, p38) within 30 min and stimulated expression of several inflammatory response genes by 2 h. MAPK signaling was extinguished by 6 h infection, and there was a dramatic reduction of secreted TNF-alpha, IL-6, and IL-8 in the absence of DC death. This corresponded temporally with enzymatic cleavage of proximal MAPK signaling proteins (MEK-1, MEK-3, and MAP kinase kinase-4) and may indicate activity of anthrax lethal toxin. Taken together, these results suggest that B. anthracis may exploit DCs to facilitate infection.
...
PMID:Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis. 1584 53

A disease-related, corticosteroid-insensitive increase in the expression of epidermal growth factor (EGF) receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium has been shown previously by the current authors. To determine whether this is associated with enhanced intracellular signalling, the aim of this study was to evaluate epithelial tyrosine phosphorylation. Bronchial biopsies were analysed for the presence of phosphotyrosine by immunohistochemistry. Bronchial epithelial cells were exposed to EGF, hydrogen peroxide or tumour necrosis factor-alpha in vitro for measurement of tyrosine phosphorylated signalling intermediates and interleukin (IL)-8 release. Phosphotyrosine was increased significantly in the epithelium of severe asthmatics when compared with controls or mild asthmatics; however, in mild asthma, phosphotyrosine levels were significantly decreased when compared with controls. There was no significant difference between phosphotyrosine levels before or after 8 weeks of treatment with budesonide. Stimulation of bronchial epithelial cells resulted in tyrosine phosphorylation of several proteins, including EGFR, Shc and p42/p44 mitogen-activated protein kinase. In the presence of salbutamol, a transient partial suppression of EGFR phosphorylation occurred, whereas dexamethasone was without effect. Neither salbutamol nor dexamethasone inhibited EGF-stimulated IL-8 release. These data indicate that regulation of protein tyrosine kinase activity is abnormal in severe asthma. The epidermal growth factor receptor and/or other tyrosine kinase pathways may contribute to persistent, corticosteroid-unresponsive inflammation in severe asthma.
...
PMID:Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium. 1592 44

The heterophil is the major polymorphonuclear cell in birds with a functional capacity akin to that of the mammalian neutrophil. Herein, we demonstrate that heterophils constitutively express TLR1/6/10, TLR2 type 1, TLR2 type 2, TLR3, TLR4, TLR5, and TLR7 mRNA. Furthermore, TLR agonists, including flagellin (from Salmonella typhimurium, FGN), peptidoglycan (from Staphylococcus aureus, PGN), ultra-pure lipopolysaccharide (from Salmonella minnesota, LPS), the synthetic double stranded RNA analog [poly(I:C)], and the guanosine analog, loxoribine (LOX) directly induced both an oxidative burst and a degranulation response. Interestingly, the synthetic bacterial lipoprotein Pam3CSK4 (palmitoyl-3-cysteine-serine-lysine-4, PAM) induced degranulation, but no oxidative burst. The bacterial TLR agonists (PAM, PGN, LPS, and FGN) all induced an up-regulation of expression of mRNA of the pro-inflammatory cytokines IL-1beta, IL-6, and IL-8; whereas both poly(I:C) and LOX induced a down-regulation of these cytokine mRNAs. Stimulation of heterophils with each specific TLR agonist led to a differential increase in the phosphorylation of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation, but not the phosphorylation of c-Jun NH2-terminal kinase (JNK). The broad TLR expression profile in heterophils reflects their principal role as first line effector cells in avian host defense against bacterial, viral, fungal, and parasitic infections. The results demonstrate the differential involvement of TLR-induced signals in the stimulation of transduction pathways that regulate the oxygen-dependent and -independent antimicrobial defense mechanisms of avian heterophils.
...
PMID:Expression and function of Toll-like receptors in chicken heterophils. 1593 35

Chemokines, or chemotactic cytokines, are major regulators of the inflammatory response and have been identified as pathogenic factors in the periprosthetic soft tissue. Particulate wear debris induced NF-kappaB activation, the major transcriptional regulator of IL-8 and MCP-1 pro-inflammatory genes and, indeed, both IL-8 and MCP-1 chemokine gene expressions were upregulated in titanium particulate-stimulated human osteoblasts. Here, we demonstrate that phagocytosed particles activate the IL-8 gene promoter via a NF-kappaB-mediated mechanism. Transfection of a dominant negative mutant IkappaBalpha protein that cannot be serine phosphorylated led to suppression of IL-8 promoter activity. The p65/RelA NF-kappaB subunit activity was affected in both a time- and titanium particle concentration-dependent fashion. Titanium particles led to increased ERK, JNK, and p38 activation in MG-63 osteoblast cells, and IL-8 protein release was suppressed by specific inhibitors of the ERK and p38 MAPK pathways. Together, our results suggest that wear debris particles induce chemokine expression in osteoblasts via NF-kappaB-mediated transcriptional activation, which is controlled by the MAPK signal transduction pathway.
...
PMID:Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by NF-kappaB. 1595 Apr 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---