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Host Genes (host + gene)
Selected AbstractsGene expression of AGS cells stimulated with released proteins by Helicobacter pyloriJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008Nayoung Kim Abstract Background and Aim:, Interactions between released proteins by Helicobacter pylori (H. pylori) and the cells of gastric epithelium to which it adheres may contribute to gastric inflammation and epithelial damage. The present study was performed to evaluate the gene expression of AGS gastric cancer cells stimulated with released proteins by H. pylori. Methods:, Gene expression of AGS cells to the stimulation by H. pylori -released proteins (G27 strain) were monitored using oligonucleotide microarrays. Results:, Eighty-eight genes (0.88%) and eight genes (0.08%) were up- or downregulated, respectively, by treating AGS cells with H. pylori -released proteins but not by H. pylori adhesion after 12 h of coculture. Out of the selected 40 up- and five downregulated genes, 29 upregulated genes classified as general RNA polymerase II transcription factor activity (GTF2B, PPARGC1A), SH3/SH2 adaptor activity (CRKL), transferase activity (ACLY, CRKL, PIGC, PLK4), and oxidoreductase activity (IDH1) were confirmed to be upregulated by released proteins and not by H. pylori adhesion by real-time reverse transcription,polymerase chain reaction. When the concentrated H. pylori -cultured supernatant prepared by our protocol was treated by boiling, the upregulations of 26 of these 29 genes (89.7%) except for CD160, ZNF268, and PSAT1 disappeared. This confirmed that most of these upregulations were caused by released proteins. Conclusion:, Host genes involving transcription, signaling and stress are significantly modulated by the proteins released by H. pylori. This might strengthen the gastroduodenal pathogenesis induced by H. pylori. [source] Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation indexHISTOPATHOLOGY, Issue 6 2004B Azzimonti Aims:, To investigate whether the expression of interferon (IFN)-inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. Methods:, Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. Results:, HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. Conclusions:, To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. [source] Low expression of the interleukin (IL)-4 receptor alpha chain and reduced signalling via the IL-4 receptor complex in human neonatal B cellsIMMUNOLOGY, Issue 1 2006Cuixia Tian Summary Diminished neonatal antibody responses following infection or immunization may stem in part from intrinsic characteristics of neonatal B cells. In this study, we used B-cell subset sorting combined with gene expression assays to investigate major differences in the expression of host genes in neonatal and adult naïve B cells. We discovered significantly reduced expression of the interleukin (IL)-4 receptor alpha chain and reduced IL-4-induced signalling in neonatal B cells. Neonatal naïve B cells were susceptible to more rapid and more profound levels of apoptosis when cultured in vitro. They also exhibited a limited response to IL-4 treatment compared with adult cells. The expression level of the IL-13 receptor alpha 1 chain, a key component of the IL-13 receptor/IL-4 type II receptor, and the response to IL-13 treatment for protection against apoptosis in neonatal B cells were similar to those of the adult B cells. These studies suggest a possible mechanism underlying the limited magnitude and durability of neonatal antibody responses. [source] Correlated expression patterns of microRNA genes with age-dependent behavioural changes in honeybeeINSECT MOLECULAR BIOLOGY, Issue 4 2010S. K. Behura Abstract The hive-living honeybees (Apis mellifera) show age-dependent behavioural changes; young bees usually nurse the broods in the colony and the older bees engage in foraging activities. These developmentally regulated behavioural changes were previously shown to be correlated with genome-wide transcriptional changes in the honeybee brain. The indigenous small regulatory RNA molecules, known as microRNAs (miRNAs), are potent regulators of gene expression and also are developmentally regulated. Thus, we wanted to study if there might be correlation of differential expression of miRNA genes in the brain with age-dependent behavioural changes of the bees. We determined expression patterns of a set (n= 20) of predicted miRNA genes, by quantitative real-time PCR assays, in the brains of young and old bees that were engaged in nursing or foraging activities in the colony, respectively. Our data show correlated up-regulation of miRNA-124, miRNA-14, miRNA-276, miRNA-13b, let-7 and miRNA-13a in the young nurse bees. miRNA-12, miRNA-9, miRNA-219, miRNA-210, miRNA-263, miRNA-92 and miRNA-283 showed correlated expression patterns in the old forager bees. The modular changes of miRNA genes in the young nurse and old forager bees suggest possible roles of miRNAs in age-dependent behavioural changes in bees. The correlated expression of intronic miRNA genes and their host genes as well as of miRNA genes physically clustered in the genome are also observed. [source] Tannerella forsythia infection-induced calvarial bone and soft tissue transcriptional profilesMOLECULAR ORAL MICROBIOLOGY, Issue 5 2010V. Bakthavatchalu Summary Tannerella forsythia is associated with subgingival biofilms in adult periodontitis, although the molecular mechanisms contributing to chronic inflammation and loss of periodontal bone remain unclear. We examined changes in the host transcriptional profiles during a T. forsythia infection using a murine calvarial model of inflammation and bone resorption. Tannerella forsythia was injected into the subcutaneous soft tissue over calvariae of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated and Murine GeneChip® (Affymetrix, Santa Clara, CA) array analysis of transcript profiles showed that 3226 genes were differentially expressed in the infected soft tissues (P < 0.05) and 2586 genes were differentially transcribed in calvarial bones after infection. Quantitative real-time reverse transcription-polymerase chain reaction analysis of transcription levels of selected genes corresponded well with the microarray results. Biological pathways significantly impacted by T. forsythia infection in calvarial bone and soft tissue included leukocyte transendothelial migration, cell adhesion molecules (immune system), extracellular matrix,receptor interaction, adherens junction, and antigen processing and presentation. Histologic examination revealed intense inflammation and increased osteoclasts in calvariae compared with controls. In conclusion, localized T. forsythia infection differentially induces transcription of a broad array of host genes, and the profiles differ between inflamed soft tissues and calvarial bone. [source] Molecular characterization of Treponema denticola infection-induced bone and soft tissue transcriptional profilesMOLECULAR ORAL MICROBIOLOGY, Issue 4 2010V. Bakthavatchalu Summary Treponema denticola is associated with subgingival biofilms in adult periodontitis and with acute necrotizing ulcerative gingivitis. However, the molecular mechanisms by which T. denticola impacts periodontal inflammation and alveolar bone resorption remain unclear. Here, we examined changes in the host transcriptional profiles during a T. denticola infection using a murine calvarial model of inflammation and bone resorption. T. denticola was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and the calvarial bones were excised. RNA was isolated and analysed for transcript profiling using Murine GeneChip® arrays. Following T. denticola infection, 2905 and 1234 genes in the infected calvarial bones and soft tissues, respectively, were differentially expressed (P , 0.05). Biological pathways significantly impacted by T. denticola infection in calvarial bone and calvarial tissue included leukocyte transendothelial migration, cell adhesion (immune system) molecules, cell cycle, extracellular matrix,receptor interaction, focal adhesion, B-cell receptor signaling and transforming growth factor-, signaling pathways resulting in proinflammatory, chemotactic effects, and T-cell stimulation. In conclusion, localized T. denticola infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed calvarial bone and soft tissues. [source] Plant virus infection-induced persistent host gene downregulation in systemically infected leavesTHE PLANT JOURNAL, Issue 2 2008Zoltán Havelda Summary Understanding of virus infection-induced alterations in host plant gene expression and metabolism leading to the development of virus disease symptoms is both scientifically and economically important. Here, we show that viruses belonging to various RNA virus families are able to induce efficient host gene mRNA downregulation (shut-off) in systemically infected leaves. We demonstrate that the host gene mRNA shut-off overlaps spatially with virus-occupied sectors, indicating the direct role of virus accumulation in this phenomenon. The establishment of shut-off was not directly connected to active viral replication or the RNA-silencing machinery. Importantly, the induced shut-off phenomenon persisted for several weeks, resulting in severe deficiency of mRNA for important housekeeping genes in the infected plants. Interestingly, we found that some other RNA viruses do not induce or only slightly induce the shut-off phenomenon for the same set of genes, implicating genetic determination in this process. Nuclear run-on experiments suggest that plant viruses, similarly to animal viruses, mediate suppression of host mRNA synthesis in the nucleus. By investigating various host,virus interactions, we revealed a correlation between the intensity of the shut-off phenomenon and the severity of disease symptoms. Our data suggest that efficient and persistent downregulation of host genes may be an important component of symptom development in certain host,virus interactions. [source] Illuminating the host , How RNAi screens shed light on host-pathogen interactionsBIOTECHNOLOGY JOURNAL, Issue 6 2009Miguel Prudêncio Abstract Over millions of years pathogens have coevolved with their respective hosts utilizing host cell functions for survival and replication. Despite remarkable progress in developing antibiotics and vaccination strategies in the last century, infectious diseases still remain a severe threat to human health. Meanwhile, genomic research offers a new era of data-generating platforms that will dramatically enhance our knowledge of pathogens and the diseases they cause. Improvements in gene knockdown studies by RNA interference (RNAi) combined with recent developments in instrumentation and image analysis enable the use of high-throughput screening approaches to elucidate host gene functions exploited by pathogens. Although only a few RNAi-based screens focusing on host genes have been reported so far, these studies have already uncovered hundreds of genes not previously known to be involved in pathogen infection. This review describes recent progress in RNAi screening approaches, highlighting both the limitations and the tremendous potential of RNAi-based screens for the identification of essential host cell factors during infection. [source] Antimalarial drugs , host targets (re)visitedBIOTECHNOLOGY JOURNAL, Issue 3 2006Margarida Cunha-Rodrigues Abstract Every year, forty percent of the world population is at risk of contracting malaria. Hopes for the erradication of this disease during the 20th century were dashed by the ability of Plasmodium falciparum, its most deadly causative agent, to develop resistance to available drugs. Efforts to produce an effective vaccine have so far been unsuccessful, enhancing the need to develop novel antimalarial drugs. In this review, we summarize our knowledge concerning existing antimalarials, mechanisms of drug-resistance development, the use of drug combination strategies and the quest for novel anti-plasmodial compounds. We emphasize the potential role of host genes and molecules as novel targets for newly developed drugs. Recent results from our laboratory have shown Hepatocyte Growth Factor/MET signaling to be essential for the establishment of infection in hepatocytes. We discuss the potential use of this pathway in the prophylaxis of malaria infection. [source] Coxiella burnetii inhabits a cholesterol-rich vacuole and influences cellular cholesterol metabolismCELLULAR MICROBIOLOGY, Issue 3 2006Dale Howe Summary Coxiella burnetii directs the synthesis of a large parasitophorous vacuole (PV) required for replication. While some lysosomal characteristics of the PV have been described, the origin and composition of the PV membrane is largely undefined. Cholesterol is an essential component of mammalian cell membranes where it plays important regulatory and structural roles. Here we investigated the role of host cholesterol in biogenesis and maintenance of the C. burnetii PV in Vero cells. The C. burnetii PV membrane stained with filipin and was positive for the lipid raft protein flotillin-1, suggesting PV membranes are enriched in cholesterol and contain lipid raft microdomains. C. burnetii infection increased host cell cholesterol content by 1.75-fold with a coincident upregulation of host genes involved in cholesterol metabolism. Treatment with U18666A, lovastatin, or 25-hydroxycholesterol, pharmacological agents that inhibit cholesterol uptake and/or biosynthesis, altered PV morphology and partially inhibited C. burnetii replication. Complete inhibition of C. burnetii PV development and replication was observed when infected cells were treated with imipramine or ketoconazole, inhibitors of cholesterol uptake and biosynthesis respectively. We conclude that C. burnetii infection perturbs host cell cholesterol metabolism and that free access to host cholesterol stores is required for optimal C. burnetii replication. [source] Temporal cytokine gene expression patterns in subjects with trachoma identify distinct conjunctival responses associated with infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2005N. Faal Summary Ocular chlamydial disease is clinically diagnosed by the appearance of characteristic inflammatory changes and development of lymphoid follicles in the conjunctiva. Nucleic acid amplification tests and relatively non-invasive methods of sampling the conjunctival surface can be used to quantify the expression of chlamydial and host genes. Using quantitative real-time polymerase chain reaction to detect the presence of Chlamydia trachomatis (CT) 16S rRNA and human interleukin (IL)-1,, IL-10, IL-12p40, interferon (IFN)-, and tumour necrosis factor (TNF)-, transcripts we examined the immune response at the conjunctival surface in a cohort of children living in a trachoma-endemic village in The Gambia. Elevated cytokine transcript levels were associated with the presence of CT 16S rRNA. Subclinical infection (CT infection without clinical signs of disease) elicited an immune response that is proinflammatory in nature, with elevations in the transcription of IL-1,, IFN-, and IL-12p40. Clinically apparent infections were associated with the elevation of mRNA for the multi-functional cytokine TNF-, (fibrotic, type 1 inflammatory and regulatory) and the counter regulatory cytokine, IL-10, in addition to the other proinflammatory cytokines. A positive correlation between IFN-, transcript levels and the amount of CT 16S rRNA expressed in conjunctiva was found. [source] | |||||||||||||