Dendritic cells (DCs) are first responders of the innate immune system that integrate signals from external stimuli to direct context-specific responses. Current models suggest an active switch mitochondrial metabolism glycolysis accompanies DC activation support anabolic requirements function. We show early glycolytic is a common program for both strong and weak stimuli, but weakly activated DCs lack long-term HIF-1α-dependent reprogramming retain oxidative metabolism. Early induction...

Epstein-Barr virus (EBV) utilizes a completely different mode of DNA replication during the lytic cycle than that employed latency. The latency origin replication, ori-P, which functions in latent episomal form EBV genome, requires only single virally encoded protein, EBNA-1, for its activity. During cycle, separate origin, ori-Lyt, is utilized. Relatively little known about trans-acting proteins involved ori-Lyt replication. We established cotransfection-replication assay to identify genes...

Using a transient replication assay in which cosmid DNAs were cotransfected into Vero cells, we had previously demonstrated that oriLyt required six Epstein-Barr virus (EBV)-encoded genes. No origin-binding protein was identified this study, but the cotransfection also dependent on three lytic cycle transactivators Zta, Rta, and Mta an activity encoded by EBV Sal/I F fragment. We have now used expression plasmids for known proteins to further examine question of requirement protein. The...

Hepatocyte growth factor/scatter factor is a multifunctional that induces mitogenesis, motility, invasion, and branching tubulogenesis of several epithelial endothelial cell lines in culture. The receptor for hepatocyte has been identified as the Met-tyrosine kinase. Upon stimulation with factor, Met β subunit becomes highly phosphorylated on tyrosine residues, one which, 1356 within carboxyl terminus, crucial dissociation, tubule formation Madin-Darby canine kidney cells. Tyrosine forms...

Airway smooth muscle (ASM) growth contributes to the mechanism of airway hyperresponsiveness in asthma. Here we demonstrate that CD4+ T cells, central chronic inflammation, drive ASM remodeling experimental Adoptive transfer cells from sensitized rats induced an increase proliferation and inhibition apoptosis myocytes naive recipients upon repeated antigen challenge, which resulted mass. Genetically modified expressing enhanced GFP (EGFP) were localized by confocal microscopy juxtaposition...

The met proto-oncogene is a receptor tyrosine kinase for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF multifunctional cytokine that stimulates mitogenesis, motility, invasion, and tubulogenesis of spectrum epithelial endothelial cells in culture. Using chimeric (CSF-MET), containing the extracellular domain colony stimulating factor-1 (CSF-1) fused to transmembrane intracellular Met receptor, we have previously demonstrated activation sufficient mediate invasion morphogenic...

The Tpr-Met oncoprotein, which is a member of family tyrosine kinase oncoproteins generated following genomic rearrangement, consists the catalytic domain hepatocyte growth factor/scatter factor receptor (Met) fused downstream from sequences encoded by tpr gene. We have previously demonstrated that single residue in carboxyl terminus, Tyr489, highly phosphorylated and essential for efficient transformation Fr3T3 fibroblasts association with Grb2 adaptor protein phosphatidylinositol...

The Tpr-Met oncoprotein consists of the catalytic kinase domain hepatocyte growth factor/scatter factor receptor tyrosine (Met) fused downstream from sequences encoded by the<i>tpr</i> gene. is a member family oncoproteins generated following genomic rearrangement and has constitutive activity. We have previously demonstrated that single carboxyl-terminal residue, Tyr⁴⁸⁹, essential for efficient transformation Fr3T3 fibroblasts forms multisubstrate binding site Grb2,...

The Zta transactivator is crucial for both Epstein-Barr virus (EBV) lytic gene expression and DNA replication. We have used a cotransfection-replication assay to examine the effect of mutations in activation domain (amino acids [aa] 1 167) on replication activity. Deletion aa 25 86, which are critical transcriptional ori-Lyt, or 93 141 did not adversely affect an ori-Lyt-containing target plasmid. However, removal 2 (delta2-25) abolished Within this subdomain, deletion 10 (delta2-10)...

Abstract Allergic airways disease is initiated and perpetuated by an aberrant Th2 inflammatory response regulated in part the cytokines IL-4 IL-13, each of which induces activation STAT-6 transcription factor. Data from murine models indicate that clinical manifestations acute asthma are dependent, thus, a target for drug development allergic disease. We designed novel chimeric peptide (STAT-6 inhibitory (STAT-6-IP)) comprised sequence predicted to bind inhibit STAT-6, fused protein...

The Th2 cytokine IL-13 regulates several aspects of the asthmatic phenotype, including airway inflammation, hyperresponsiveness, and mucus production. Th17 IL-17A is also implicated in asthma has been shown to both positively negatively regulate Th2-dependent responses murine models allergic airways disease. Our objective this study was better understand role IL-17 inflammation by examining how modifies IL-13-induced inflammatory responses. We treated BALB/c mice intranasally with or alone...

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) have been suggested to be involved in the pathogenesis asthma. Their expression airway smooth muscle (ASM) cells could collagen turnover migration these thus may contribute remodelling.To examine effect pro-fibrotic growth factors TGF-beta platelet-derived factor (PDGF) on MMPs/TIMPs cultured human ASM role MMP cells.ASM were stimulated with and/or PDGF. Expression activity MMP-1, MMP-2, MMP-3, TIMP-1 TIMP-2...

Th2 immune responses are linked primarily to mild and moderate asthma, while Th17 cells, Interleukin-17A (IL-17) neutrophilia have been implicated in more severe forms of disease. How Th2-dependent allergic reactions influenced by IL-17-γδ T cells is poorly understood. In murine models, under some conditions, IL-17 promotes Th2-biased airway inflammatory responses. However, the inhibition resolution inflammation hyperresponsiveness (AHR). We compared Balb/c mice sensitized OVA with (and...

ABSTRACT Herpesviruses encode a set of core proteins essential for lytic replication their genomes. Three these form tripartite helix-primase complex that, in the case Epstein-Barr virus (EBV), consists helicase BBLF4, primase BSLF1, and linker protein BBLF2/3. BBLF2/3 its homologs other herpesviruses remain relatively poorly characterized. To better understand contribution to made by BBLF2/3, yeast two-hybrid screen was performed with as bait protein. This identified interactors number cell...

The peptide, endothelin-1 (ET-1) regulates proliferative responses in numerous cell types. Recently, a dual ET receptor antagonist was shown to prevent the increase airway smooth muscle cell(SMC) proliferation that accompanies remodeling rat model of experimental asthma. Thus, we used [3H]-thymidine incorporation assays and western immunoblotting identify signaling pathways regulate cultured tracheal SMC. Our data indicate ET-1 activation A subtype induced ERK 1/2 primary ET-1-induced were...

Treatment of allergic airways disease including asthma remains primarily local immunosuppression with topical corticosteroid and symptomatic management antihistamines anti-leucotrienes. We have developed a novel therapy designed to specifically inhibit the events associated Th2 cell activation.We assessed efficacy our cell-penetrating STAT-6 inhibitory peptide (STAT-6-IP), treatment for disease, in model chronic ragweed-induced asthma.Six- eight-week-old mice were sensitized over 5 weeks...

Sex differences in asthma prevalence are well documented but poorly understood. Murine models have contributed to our understanding of mechanisms that could regulate this sex disparity, though the majority these studies examined responses present after Th2 adaptive immunity is established. We now investigated how influences acute activation innate cell populations lung upon initial exposure model antigen, ovalbumin (OVA), presence IL-33 (OVA+IL-33), prime lungs for type 2 immunity. also...

Abundant data indicate that pathogenesis in allergic airways disease is orchestrated by an aberrant T-helper 2 (Th2) inflammatory response. CD4(+) T cells have been localized to airway smooth muscle (ASM) both human asthmatics and rodent models of disease, where they implicated proliferative responses ASM. Whether also alter ASM contractility has not addressed. We established vitro system assess the ability antigen-stimulated modify contractile Brown Norway rat trachealis muscle. Our...

Respiratory syncytial virus (RSV)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. Early life RSV infection results in a Th2-biased immune response, which also typical Murine models neonatal have been developed to examine possible contribution RSV-driven Th2 responses airway hyper-responsiveness later childhood. We investigated ability cell-penetrating STAT6 inhibitory peptide (STAT6-IP), when delivered selectively infection, modify...

The regulatory properties of B cells have been studied in autoimmune diseases; however, their role allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial cell function. Mice deficient Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and Th2 cytokines. This phenotype was reproduced by mixed bone marrow chimeric mice only cells, indicating lymphocytes were...