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)

Psoriasis is a common chronic skin disease mediated by cellular immune mechanisms and characterized by an intense neutrophil cell infiltrate and proliferative activation of epidermal keratinocytes. We have previously described the expression of the inducible nitric oxide synthase (iNOS) in epidermal keratinocytes of psoriatic skin lesions. In this study, the role of iNOS in psoriatic inflammation was explored ex vivo in psoriatic skin biopsies and in vitro in primary cultures of human keratinocytes. Messenger RNA for the iNOS enzyme (iNOS mRNA) was detected by reverse transcriptase polymerase chain reaction in skin biopsies from patients with psoriasis, but not in skin specimens from patients with atopic eczema or from healthy volunteers. As demonstrated by in situ hybridization and immunohistochemistry, expression of iNOS mRNA and its gene product was localized to the epidermal keratinocytes of psoriatic skin lesions. In situ hybridization further revealed a complete colocalization of mRNA expression for iNOS with interleukin (IL) 8 receptor-specific mRNA either in the basal germinative cell layer or at focal sites of ongoing neutrophil inflammation in suprabasal cell layers. Because psoriatic keratinocytes have previously been shown to express mRNA transcripts for IL-8, it seemed reasonable to hypothesize that iNOS expression could be induced in an autocrine loop by IL-8. This hypothesis was substantiated by our in vitro experiments showing that a combination of IL-8 and interferon gamma induces the expression of iNOS-specific mRNA and of the functional enzyme in cultured human keratinocytes. These results suggest an important role for iNOS in concert with IL-8 and its receptor early during the formation of psoriatic lesions.
 ...
PMID:A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes. 892 Aug 87

Our previous studies have shown a different pattern of immediate early gene and growth factor gene expression between compensatory liver regeneration occurring after cell loss/death and direct hyperplasia induced by primary mitogens. In the present study, modifications in the activation of two transcription factors, NF-kappaB and AP-1; steady-state levels of tumor necrosis factor alpha (TNF-alpha) messenger RNA (mRNA); and induction of the inducible nitric oxide synthase (iNOS) were examined in rat liver during different types of cell proliferation. Compensatory regeneration was induced in male Wistar rats by partial hepatectomy of two thirds (PH) or a necrogenic dose of CCl4 (2 mL/kg), whereas direct hyperplasia was induced by a single administration of the primary mitogens lead nitrate (LN, 100 micromol/kg), cyproterone acetate (CPA, 60 mg/kg), or nafenopin (NAF, 200 mg/kg). Liver regeneration after treatment with CCl4 was associated with an increase in steady-state levels of TNF-alpha mRNA, activation of NF-kappaB and AP-1, and induction of iNOS. A strong and prolonged activation of NF-kappaB but not of AP-1 was observed in LN-induced hyperplasia. LN also induced an increase in hepatic levels of TNF-alpha and iNOS mRNA. On the other hand, direct hyperplasia induced by two other primary mitogens, NAF and CPA, occurred in the complete absence of modifications in the hepatic levels of TNF-alpha mRNA, activation of NF-kappaB and AP-1, or induction of iNOS, although the number of hepatocytes entering S phase 18 to 24 hours after NAF was similar to that seen after PH. These results add further support to the hypothesis that cell proliferation occurring in the absence of cell loss/death may be triggered by unknown signaling pathways different from those responsible for the transition of hepatocytes from G0 to G1 after PH or cell necrosis.
 ...
PMID:Liver cell proliferation induced by nafenopin and cyproterone acetate is not associated with increases in activation of transcription factors NF-kappaB and AP-1 or with expression of tumor necrosis factor alpha. 904 3

Selectin-P expression on platelets stimulated with thrombin was measured in terms of formation of "rosettes" according to Jungi et al. [9]. Selectin-P-mediated platelet/PMNs adhesion was inhibited by iloprost (IC50 = 5.0 nM), sodium nitroprusside (NaNP, IC50 = 0.93 microM) and interleukin-8 (IL-8, IC50 = 88 ng/ml), but activated dose-dependently by oxy-LDL (3-15 micrograms/ml). Glycogen-induced peritonitis in rats up-regulated the iNOS activity measured by the 2,3-[3H]-citrulline formation by the abdominal cavity PMNs up to 6 h after insult. Pretreatment with IL-8 (3 micrograms/300 g iv) decreased the amount of PMNs in ascites as well as its iNOS activity. Chemotaxis mediated iNOS gene expression of PMNs were measured by Northern blot hybridization. IL-8 (100 ng/ml) did not influence the PMNs iNOS gene expression induced by chemotaxis. We conclude that the decrease in iNOS activity by IL-8 involves postranslational modification of the enzyme activity.
 ...
PMID:Influence of oxy-LDL and interleukin-8 on the platelet/PMNs adhesion and on chemotaxis-mediated induction of iNOS in neutrophils. 911 35

During immune injury, activation of endothelial cells by inflammatory cytokines stimulates leukocyte adhesion to the endothelium, turns the endothelium from an anticoagulant surface to one that is frankly procoagulant, and results in the release of vasoactive mediators and growth factors. Cytokine activation of endothelial cells also results in increased endothelial cell TGF-beta 1 synthesis and enhanced activation of latent TGF-beta, the latter involving a shift of plasmin production from the apical to subendothelial surface. In cytokine-stimulated endothelial cells, TGF-beta hinders leukocyte adhesion and transmigration via inhibition of IL-8 and E-selectin expression. TGF-beta also profoundly diminishes cytokine-stimulated inducible nitric oxide synthase production and instead augments endothelial nitric oxide synthase expression. Thus, some of the TGF-beta actions on endothelium during immune activation can viewed as immunosuppressive. TGF-beta also influences mechanisms of vascular remodeling during the healing phase of immune injury. It stimulates PDGF-B synthesis by endothelial cells, causes bFGF release from subendothelial matrix, and promotes VEGF synthesis by non-endothelial cells. Together these mediators control angiogenesis, a critical component of the vascular repair phenomenon. Further, endothelial cell derived PDGF-B and bFGF influence the proliferation and migration of neighboring cells. Thus, endothelial cells and TGF-beta actions on the endothelium play important roles both during the initial phase of immune injury and during the later remodeling phase.
 ...
PMID:TGF-beta and the endothelium during immune injury. 915 Apr 51

Air pollution, in particular that generated by road traffic, is a matter of rising public concern and has been implicated in the worsening of asthma. In this article, the evidence that air pollutants (particularly sulphur dioxide, ozone and nitrogen dioxide) can affect the airways of asthmatic patients is reviewed, and the possible molecular mechanisms that may link air pollution to increased inflammation in the airways are discussed. Airway epithelial cells may respond to oxidant pollutants by the activation of transcription factors, such as nuclear factor kappa B, resulting in increased transcription of genes for certain cytokines, such as interleukin 8 and inflammatory enzymes, such as inducible nitric oxide synthase and cyclo-oxygenase.
 ...
PMID:Air pollution and asthma: molecular mechanisms. 941 51

The aim of the present study was to determine the efficacy of a new combination regimen including an antioxidant, a proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastric inflammation. From 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for the experimental measures. The patients were then treated either with lansoprazole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially so in the LAM group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradication regimen against H. pylori has advantages either in augmenting the eradication rates of H. pylori or in decreasing the oxidative stress and cytokines levels generated by H. pylori infection.
 ...
PMID:Augmented eradication rates of Helicobacter pylori by new combination therapy with lansoprazole, amoxicillin, and rebamipide. 951 12

Epithelial cells are the first point of host contact for invasive intestinal pathogens and may initiate mucosal inflammatory responses via production of proinflammatory cytokines and mediators. The aim of the present study was to investigate in vitro the initial invasion of a parasitic nematode (Trichinella spiralis), to measure the early production of specific epithelial cytokines and inflammatory mediators after invasion, and to compare these responses with those to invasive bacteria. Monolayers of human colonic epithelial cell lines (HT29, T84, and Caco-2) were infected by T. spiralis or Listeria monocytogenes. Bile-activated infective larvae of T. spiralis invaded and migrated into the epithelial cell monolayers, leaving trails of dead cells. Transmission electron microscopy studies of damaged cells along the trail showed a progressive increase in size, disruption of cell membranes, loss or dilution of cytoplasmic proteins, and swelling of mitochondria and nuclei. However, no nuclear fragmentation was observed. With reverse transcription-PCR and an enzyme-linked oligonucleotide chemiluminescent assay, mRNA transcripts of interleukin-1beta (IL-1beta), IL-8, and epithelial neutrophil-activating peptide 78 were shown to increase in epithelial cells invaded by T. spiralis or L. monocytogenes, but only L. monocytogenes elicited increased inducible nitric oxide synthase (iNOS) mRNA. No increase in tumor necrosis factor alpha or transforming growth factor beta mRNA was seen after T. spiralis invasion. Increased levels of IL-8 were also released from the basolateral surfaces of infected monolayers as detected by sandwich enzyme-linked immunosorbent assay. Induction and secretion of proinflammatory cytokines in epithelial cells after nematode or bacterial invasion may initiate the acute inflammatory response of the small intestine. The upregulation of iNOS in bacterial infections may contribute to mucosal defense and may also be associated with subsequent cell death, whereas different mechanisms appear to operate after nematode invasion.
 ...
PMID:Production of proinflammatory cytokines and inflammatory mediators in human intestinal epithelial cells after invasion by Trichinella spiralis. 957 8

The aim of the present study was to determine the efficacy of a new combination regimen including antioxidant, proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastritis. From each of 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection, five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for experimental measures. The patients were then treated either with lansoprozole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) -mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially in the LAM-treated group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of the antioxidative drug rebamipide to the eradication regimen against H. pylori has quantitative and qualitative advantages such as either augmenting the eradication rates of H. pylori or decreasing oxidative stress and cytokines levels generated by H. pylori infection.
 ...
PMID:Quantitative and qualitative usefulness of rebamipide in eradication regimen of Helicobacter pylori. 975 49

We hypothesized that blocking the induction of proinflammatory genes associated with endothelial cell (EC) activation, by inhibiting the transcription factor nuclear factor kappaB (NF-kappaB), would prolong survival of vascularized xenografts. Our previous studies have shown that inhibition of NF-kappaB by adenovirus-mediated overexpression of I kappaB alpha suppresses the induction of proinflammatory genes in EC. However, I kappaB alpha sensitizes EC to TNF-alpha-mediated apoptosis, presumably by suppressing the induction of the NF-kappaB-dependent anti-apoptotic genes A20, A1, manganese superoxide dismutase (MnSOD), and cellular inhibitor of apoptosis 2. We report here that adenovirus mediated expression of a dominant negative C-terminal truncation mutant of p65/RelA (p65RHD) inhibits the induction of proinflammatory genes, such as E-selectin, ICAM-1, VCAM-1, IL-8, and inducible nitric oxide synthase, in EC as efficiently as does I kappaB alpha. However, contrary to I kappaB alpha, p65RHD does not sensitize EC to TNF-alpha-mediated apoptosis although both inhibitors suppressed the induction of the anti-apoptotic genes A20, A1, and MnSOD equally well. We present evidence that this difference in sensitization of EC to apoptosis is due to the ability of p65RHD, but not I kappaB alpha, to inhibit the constitutive expression of c-myc, a gene involved in the regulation of TNF-alpha-mediated apoptosis. These data demonstrate that it is possible to block the expression of proinflammatory genes during EC activation by targeting NF-kappaB, without sensitizing EC to apoptosis and establishes the role of c-myc in controlling induction of apoptosis during EC activation. Finally, these data provide the basis for a potential approach to suppress EC activation in vivo in transgenic pigs to be used as donors for xenotransplantation.
 ...
PMID:Adenovirus-mediated expression of a dominant negative mutant of p65/RelA inhibits proinflammatory gene expression in endothelial cells without sensitizing to apoptosis. 979 84

Nitric oxide produced by inducible nitric oxide synthase (iNOS) has been claimed to be involved in gastritis; however, its characteristics are largely unknown. We assessed (1) iNOS expression in the human gastric mucosa in chronic gastritis and (2) the cytokines associated with iNOS expression. Gastric biopsy specimens were obtained from patients with chronic gastritis. Total RNA was isolated and reverse transcription-polymerase chain reaction (PCR) was performed semiquantitatively using specific primer sets for iNOS, interleukin (IL)-1beta, IL-8, IL-6, interferon-y, tumor necrosis factor-alpha (TNF-alpha), TNF receptors, IL-6 receptors, and sucrase, respectively. Helicobacter pylori infection was examined by the PCR assay. Reverse transcription-PCR analysis showed that expression of iNOS was detected in 10 of 23 samples. Expression of iNOS mRNA was closely correlated with expression of TNF-alpha and was observed frequently in subjects with intestinal metaplasia. The Helicobacter pylori gene was detected by PCR assay in all iNOS-positive cases. These results indicate that iNOS is predominantly expressed in the gastric mucosa with intestinal metaplasia and H. pylori infection. TNF-alpha is thought to be an important cytokine associated with iNOS expression.
 ...
PMID:Enhanced expression of inducible nitric oxide synthase in chronic gastritis with intestinal metaplasia. 980 53


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