Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus E1A DNA and proteins are frequently detected in lungs of patients with chronic obstructive pulmonary disease. Because adenovirus E1A can regulate host gene expression by interacting with cellular transcription factors, we postulate that E1A enhances synthesis of inflammatory mediators. To examine this possibility, we measured the expression of inflammatory cytokines in E1A-producing A549 human pulmonary epithelial cells and control cells. Interleukin (IL)-8 mRNA was markedly induced by lipopolysaccharide (LPS) in E1A-producing cells but not in controls. IL-8 protein levels were elevated in parallel. In both cell types, monocyte chemotactic and activating factor mRNA induced by LPS was low, and transforming growth factor-beta 1 mRNA was not affected. IL-1 beta, IL-6, granulocyte macrophage colony-stimulating factor, and granulocyte colony-stimulating factor mRNAs were too low to show any effect of E1A. We conclude that the LPS responsiveness of A549 pulmonary epithelial cells is altered by adenoviral E1A by upregulating IL-8. We speculate that this mechanism may be important in the amplification of the inflammatory process of lungs to other irritants.
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PMID:Adenovirus E1A upregulates interleukin-8 expression induced by endotoxin in pulmonary epithelial cells. 922 2

IL-17 is a novel cytokine secreted principally by CD4+ T cells. It has been shown to support the growth of hemopoietic progenitors in vitro; however, its in vivo effects are presently unknown. Adenovirus-mediated gene transfer of the murine IL-17 cDNA targeted to the liver (5 x 10(9) plaque-forming units (PFU) intravenous) resulted in a transiently transgenic phenotype, with dramatic effects on in vivo granulopoiesis. Initially, there was a significant increase (fivefold) in the peripheral white blood count (WBC), including a 10-fold rise in the absolute neutrophil count. This was associated with a doubling in the spleen size over 7-14 days after gene transfer, which returned to near baseline by day 21, although the white blood cell count remained elevated. There was a profound stimulation of splenic hemopoiesis as demonstrated by an increase in total cellularity by 50% 7 days after gene transfer and an increase in hemopoietic colony formation. A maximal increase in frequency of high proliferative potential colonies (HPPC) (11-fold) and CFU-granulocyte-macrophage (GM) and CFU-granulocyte-erythrocyte-megakaryocyte-monocyte (GEMM) (CFU) (6-fold) was seen on day 3 after IL-17 gene transfer. Both CFU and HPPC remained significantly elevated in the spleen throughout day 21, but at reduced levels compared with day 3. Bone marrow CFU and HPPC were elevated on day 3 only by 75% and 25%, respectively, without changes in total cellularity. Thus, murine IL-17 is a cytokine that can stimulate granulopoiesis in vivo. Since IL-17 is principally produced by CD4+ T cells, this cytokine could have therapeutic implications in AIDS-related bone marrow failure and opportunistic infections.
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PMID:IL-17 stimulates granulopoiesis in mice: use of an alternate, novel gene therapy-derived method for in vivo evaluation of cytokines. 983 29

Adenovirus infection of hematopoietic cells frequently requires high virus concentrations and long incubation times to obtain moderate infection levels because these cells have low levels of Coxsackie and adenovirus receptor (CAR) and alpha(v) integrin. The effect of treatment with FR901228 (depsipeptide), a histone deacetylase inhibitor in phase 2 clinical trials, was studied in K562 cells, granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells (PBMCs), and CD34+ peripheral blood stem cells (PBSCs). FR901228 increased CAR and alpha(v) integrin RNA levels and histone H3 acetylation. FR901228 treatment before adenovirus infection was associated with at least a 10-fold increase in transgene expression from a beta-galactosidase-expressing adenoviral vector. More than 80% of the PBMCs or CD34+ PBSCs from 7 different donors were beta-galactosidase-positive after adenovirus infection with a multiplicity of infection of 10 for 60 minutes. Increased CAR, alpha(v) integrin, and acetylated histone H3 levels were observed in PBMCs from a patient treated with FR901228. These studies suggest that FR901228 can increase the efficiency of adenoviral infection in hematopoietic cells.
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PMID:Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells. 1187 6

Interleukin-1beta (IL-1beta) and the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, have each been shown to play an important role in neuroinflammation. However, whether these signaling molecules interact to coordinate immune/inflammatory processes and neurodegeneration has not been investigated. Here, we show that exogenous application of IL-1beta (10 ng/ml) recruited calcineurin/NFAT (nuclear factor of activated T cells) activation in primary astrocyte-enriched cultures within minutes, through a pathway involving IL-1 receptors and L-type Ca(2+) channels. Adenovirus-mediated delivery of the NFAT inhibitor, VIVIT, suppressed the IL-1beta-dependent induction of several inflammatory mediators and/or markers of astrocyte activation, including tumor necrosis factor alpha, granulocyte/macrophage colony-stimulating factor, and vimentin. Expression of an activated form of calcineurin in one set of astrocyte cultures also triggered the release of factors that, in turn, stimulated NFAT activity in a second set of "naive" astrocytes. This effect was prevented when calcineurin-expressing cultures co-expressed VIVIT, suggesting that the calcineurin/NFAT pathway coordinates positive feedback signaling between astrocytes. In the presence of astrocytes and neurons, 48-h delivery of IL-1beta was associated with several excitotoxic effects, including NMDA receptor-dependent neuronal death, elevated extracellular glutamate, and hyperexcitable synaptic activity. Each of these effects were reversed or ameliorated by targeted delivery of VIVIT to astrocytes. IL-1beta also caused an NFAT-dependent reduction in excitatory amino acid transporter levels, indicating a possible mechanism for IL-1beta-mediated excitotoxicity. Taken together, the results have potentially important implications for the propagation and maintenance of neuroinflammatory signaling processes associated with many neurodegenerative conditions and diseases.
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PMID:Interleukin-1beta-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity. 1854 37