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)

Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.
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PMID:Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). 1530 82

Marek's disease virus (MDV) is an alpha-herpesvirus that causes rapid development of T-cell lymphomas in chickens. MDV-encoded vIL-8 is homologous to the cellular IL-8 gene, and its function in MDV pathogenesis has yet to be determined. Using overlapping cosmid clone-based technology, we have generated an MDV vIL-8 deletion mutant virus, rMd5/delta vIL-8. In vivo experiments with this mutant virus demonstrated that deletion of vIL-8 results in attenuation of the virus and induction of significantly less gross tumor, both in viscera and nerves, when compared to the parental virus. Reintroduction of the vIL-8 gene in the genome of the mutant virus restored the virulence of the virus to the wild-type levels, indicating that vIL-8 plays a role in MDV-induced pathogenesis. In this study, we show that there is a significant difference in the reduction of B cells and activation of T cells in the spleen cells of chickens inoculated with parental rMd5 and vIL-8 deletion mutant virus. These results indicate that vIL-8 is involved in the early phase of pathogenesis, presumably by attracting target cells to the initial site of infection. In addition, protection studies with the vIL-8 mutant virus showed that this mildly virulent virus protects susceptible maternal antibody-positive viruses at a higher level than the commonly used serotype 1 CVI988 vaccine. These results confirm the potential of partially attenuated viruses as vaccines against very virulent plus strains and the usefulness of recombinant DNA technology to generate the next generation of MDV vaccines.
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PMID:A Marek's disease virus vIL-8 deletion mutant has attenuated virulence and confers protection against challenge with a very virulent plus strain. 1609 23

Bacterial artificial chromosome (BAC) vectors were first developed to facilitate propagation and manipulation of large DNA fragments. This technology was later used to clone full-length genomes of large DNA viruses to study viral gene function. Marek's disease virus (MDV) is a highly oncogenic herpesvirus that causes rapid induction of T-cell lymphomas in chickens. Based on the virus's ability to cause disease in vaccinated chickens, MDV strains are classified into pathotypes, with the most virulent strains belonging to the very virulent plus (vv+) pathotype. Here we report the construction of BAC clones of 686 (686-BAC), a vv+ strain of MDV. Transfection of DNA isolated from two independent clones into duck embryo fibroblasts resulted in recovery of infectious virus. Pathogenesis studies showed that the BAC-derived 686 viruses were more virulent than Md5, a vv strain of MDV. With the use of a two-step red-mediated mutagenesis process, both copies of viral interleukin 8 (vIL-8) were deleted from the MDV genome, showing that 686-BACs were amenable to mutagenesis techniques. The generation of BAC clones from a vv+ strain of MDV is a significant step toward understanding molecular basis of MDV pathogenesis.
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PMID:Cloning of a very virulent plus, 686 strain of Marek's disease virus as a bacterial artificial chromosome. 2390 63

Stratum corneum collected by tape stripping from 10 and 24 subjects with cutaneous T-cell lymphomas (CTCL) or psoriasis, respectively, were compared using quantitative label-free mass spectrometry analysis. A non-supervised statistical analysis (Posneg NMF) based on 352 differentially expressed proteins in both CTCL and psoriasis samples was able to separate the two disease groups and finally able to identify a set of 112 proteins that contributed most and significantly to the separation when compared to non-lesional samples. In addition, Luminex assay revealed that the increase in the amount of chemokines related to the inflammatory response, and immune cell infiltration and recruitment in lesional stratum corneum in CTCL, including CXCL8, CXCL9, CXCL10, CCL27, TNF and sICAM-1 was in agreement with published data on entire skin biopsies. Proteome analysis using quantitative methods including mass spectrometry and Luminex technology offered the possibility to investigate the relevant protein signature in CTCL and may be helpful to diagnose and investigate the efficacy of treatments in clinical investigations using non-invasive methods in future.
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PMID:Proteomic analysis of stratum corneum in Cutaneous T-Cell Lymphomas and psoriasis. 3063 8