In this study, we evaluated the PK/PD and explored the efficacy of a PDE4 inhibitor, CC-11050 in a murine model of Mtb infection. Infected mouse lungs with or without CC-11050 treatment was also used to interrogate genome-wide transcriptional changes.
No associated publication
Specimen part, Time
View SamplesIron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB.
No associated publication
Sex, Specimen part, Time
View SamplesInterferon (IFN) is a unique type I IFN that is not induced by pattern-recognition response elements. IFN is constitutively expressed in mucosal tissues including the female genital mucosa. We show here that IFN induces an antiviral state in human macrophages that blocks HIV-1 replication.
IFN-<b>ε</b> protects primary macrophages against HIV infection.
Specimen part, Treatment, Time
View SamplesPyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Specimen part, Treatment, Time
View SamplesMED1 is a transcriptional coactivator for gene-specific activators involved in growth and development, we were interested in identifying MED1 target genes potentially involved in prostate development by cDNA microarray. Med1 was conditional knocked out in mice prostate. We performed cDNA microarray with two sets: (1) RNA isolated from three WT ventral prostates and three MT ventral prostates; (2) RNA isolated from three WT lateral prostates and three MT lateral prostates.
No associated publication
Age, Specimen part
View SamplesTo understand molecular mechanisms underlying the synergy of Rb loss and E2F8 loss, we used gene expression profiling to assess molecular changes in Mx1-Cre-mediated knockout (KO) mice using RNA isolated from sorted Ter119+CD71high Erythroblasts.
Inactivation of Rb and E2f8 synergizes to trigger stressed DNA replication during erythroid terminal differentiation.
Specimen part
View SamplesTumor associated mutant p53 proteins often gain new functions for tumorigenesis and tumor progression. It has been shown that mutant p53 can transcriptionally regulate a group of genes, which in turn contributes to mutant p53 gain of function. A mutant p53 interacting protein Pontin binds to mutant p53 and promotes its gain of function. This experiment tests whether the interaction of Pontin with mutant p53 regulates the transcriptional activity of mutant p53.
No associated publication
Specimen part, Cell line
View SamplesAnalysis of the transcriptome of mouse models of prostate cancer to assemble a mouse prostate cancer interactome.
Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.
Treatment
View SamplesTo investigate the role of NKX3.1 in prostate differentiation, we employed transcriptome analysis of mouse seminal vesicle (from 15-month-old Nkx3.1+/+ mice); mouse prostate (from 4-month-old Nkx3.1+/+ and Nkx3.1-/- mice); human prostate cells (RWPE1 cells engineered with empty vector (altered pTRIPZ), NKX3.1 wild type over-expression, and NKX3.1 (T164A) mutant over-expression); and tissue recombinants (generated from combining engineered mouse epithelial cells (seminal vesicle epithelial cells or prostate epithelial cells from 2-month-old mice) and rat UGS mesenchymal cells). Mouse tissue or human cells were snap frozen for subsequent molecular analysis.
Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation.
Age, Specimen part, Cell line
View SamplesOvarian granulosa cells play a central role in steroidogenesis, which is critical for female reproduction. Follicle-stimulating hormone (FSH) promotes cAMPmediated signaling to regulate granulosa cell steroidogenesis. We have shown previously that 2, 2-bis-(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE) inhibits FSH- and dibutyryl cAMP-stimulated steroidogenesis, and affects the mRNA levels of steroidogenic pathway enzymes in rat granulosa cells. However, HPTE showed a differential effect in FSH- and cAMP-stimulated cells in that HPTE more completely blocked FSH- when compared to cAMP-driven steroidogenesis. The objective of this study was to analyze the effects of HPTE on global gene expression profiles in untreated granulosa cells and those challenged with FSH or cAMP. Granulosa cells from immature rats were cultured with 0, 1, 5, or 10 M HPTE in the presence and absence of either 3 ng FSH/ml or 1 mM cAMP for 48 h. Total RNA was isolated for microarray analysis using the GeneChip Rat Genome 230 2.0 and ArrayAssist Microarray Suite. An investigation of changes in gene expression across all HPTE treatments showed that HPTE altered more genes in FSH- (~670 genes) than in cAMP-stimulated cells (~366 genes). Analysis confirmed that HPTE more effectively inhibited FSH- than cAMP-induced steroid pathway gene expression and steroidogenesis. Furthermore, expression patterns of novel genes regulating signal transduction, transport, cell cycle, adhesion, differentiation, motility and growth, apoptosis, development, and metabolism were all altered by HPTE. This study further established that HPTE exerts differential effects within the granulosa cell steroidogenic pathway, and revealed that these effects include broader changes in gene expression.
Effect of the methoxychlor metabolite HPTE on the rat ovarian granulosa cell transcriptome in vitro.
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