On D-branes in the Nappi-Witten and GMM gauged WZW models

We construct D-branes in the Nappi-Witten (NW) and Guadagnini-Martellini-Mintchev (GMM) gauged WZW models. For the $SL(2,R)\times SU(2)/U(1)\times U(1)$ NW and $SU(2)\times SU(2)/U(1)$ GMM models we present the explicit equations describing the D-brane hypersurfaces in their target spaces. In the latter case we show that the D-branes are classified according to the Cardy theorem. We also present the semiclassical mass computation and find its agreement with the CFT predictions.Comment: 16 pages, harvma

Open Strings in Exactly Solvable Model of Curved Spacetime and PP-Wave Limit

In this paper we study the superstring version of the exactly solvable string model constructed by Russo and Tseytlin. This model represents superstring theory in a curved spacetime and can be seen as a generalization of the Melvin background. We investigate D-branes in this model as probes of the background geometry by constructing the boundary states. We find that spacetime singularities in the model become smooth at high energy from the viewpoint of open string. We show that there always exist bulk (movable) D-branes by the effect of electric flux. The model also includes Nappi-Witten model as the Penrose limit and supersymmetry is enhanced in the limit. We examine this phenomenon in the open string spectrum. We also find the similar enhancement of supersymmetry can be occurred in several coset models.Comment: Latex, 32 pages, typos corrected, references added, to appear in JHEP, eq.(2.22) correcte

On the hierarchy of symmetry breaking D-branes in group manifolds

We construct the boundary WZNW functional for symmetry breaking D-branes on a group manifold which are localized along a product of a number of twisted conjugacy classes and which preserve an action of an arbitrary continuous subgroup. These branes provide a geometric interpretation for the algebraic formulation of constructing D-branes developed recently in hep-th/0203161. We apply our results to obtain new symmetry breaking and non-factorizing D-branes in the background SL(2,R) x SU(2).Comment: 34 page

A defective type 1 response to rhinovirus in atopic asthma

Background: Rhinoviruses (RVs) are the most frequent precipitants of the common cold and asthma exacerbations, but little is known about the immune response to these viruses and its potential implications in the pathogenesis of asthma.Methods: Peripheral blood mononuclear cells (PBMC) from patients with atopic asthma and normal subjects were exposed to live or inactivated RV preparations. Levels of interferon (IFN)? and interleukins IL-12, IL-10, IL-4, IL-5 and IL-13 were evaluated in the culture supernatants with specific immunoassays.Results: Exposure of PBMC to RVs induced the production of IFN?, IL-12, IL-10, and IL-13. Cells from asthmatic subjects produced significantly lower levels of IFN? and IL-12 and higher levels of IL-10 than normal subjects. IL-4 was induced only in the asthmatic group, while the IFN?/IL-4 ratio was more than three times lower in the asthmatic group.Conclusions: This evidence suggests that the immune response to RVs is not uniquely of a type 1 phenotype, as previously suggested. The type 1 response is defective in atopic asthmatic individuals, with a shift towards a type 2 phenotype in a way similar, but not identical, to their aberrant response to allergens. A defective type 1 immune response to RVs may be implicated in the pathogenesis of virus induced exacerbations of asthma

Rhinovirus-induced alterations on peripheral blood mononuclear cell phenotype and costimulatory molecule expression in normal and atopic asthmatic subjects

BackgroundRhinovirus (RV) infection is the commonest trigger of acute asthma exacerbations; however, the immune response to these viruses and any potential implications in the mechanisms leading to asthma exacerbations are not well understood.ObjectiveTo assess the effects of in vitro RV infection on the phenotype and expression of costimulatory molecules on peripheral blood mononuclear cells (PBMC) from normal and atopic asthmatic subjects, as a model for RV antigen presentation.MethodsPBMC from seven normal and seven asthmatic subjects were exposed to one infectious unit/cell of RV16 for 48 h. Surface expression of CD25, CD28, CD40, CD54, CD80, CD86 and CTLA-4 was evaluated on CD3, CD4, CD8, CD14 and CD19 PBMC subpopulations by three-colour flow cytometry.ResultsNo changes in the percentage of CD3, CD4, CD8 or CD19 were observed. CD14 was significantly reduced by the infection and this was more pronounced in normal subjects. On Th cells CTLA-4 was increased after RV infection only in the asthmatic group. Levels of CD80 and CD86 in the control cultures were lower in the asthmatic group. RV infection induced a significant increase of CD80 on monocytes and of CD86 on B cells, which occurred in both groups but were less marked in atopic asthmatic subjects.ConclusionExposure of PBMC to RV is able to activate the antigen presentation machinery. Differences between normal and atopic asthmatic individuals are compatible with the hypothesis that an aberrant immune response to RV may be involved in the development of acute exacerbations in atopic asthmatic subjects

Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects

Background Increased production of IL-4 and IL-5 and decreased production of IFN-? by CD4+ T cells has been implicated in asthma pathogenesis. However, CD8+ T cells also produce type 1 and type 2 cytokines and the relative roles of CD4+ and CD8+ T cell cytokine production in asthma have not been previously studied.Objective To determine the production of the type 1 and type 2 cytokines by CD4+ and CD8+ T cell subsets in asthmatic and normal subjects.Methods Intracellular cytokine staining for IL-4, -5, -10, -13 and IFN-? was analysed in peripheral blood CD4+ and CD8+ T cells from 24 atopic asthmatic and 20 normal subjects.Results Both subsets of T cells produced all cytokines studied and there were no significant differences between CD4+ and CD8+ T cells in their capacity to produce either type 1 or type 2 cytokines. There were significantly increased frequencies of IFN-?-positive CD4+ (13.1 ± 2.4%, vs. 7.3 ± 1.4%) and CD8+ (20.0 ± 2.9%, vs. 9.6 ± 2.1%) T cells in asthmatic subjects compared with normal subjects (P < 0.05), but not in frequencies of CD4+ or CD8+ T cells staining positively for IL-4, -5, -10 or -13.Conclusion The frequencies of peripheral blood CD8+ T cells producing type 1 and type 2 cytokines are comparable with the frequencies of CD4+ T cells. There was an increased frequency of IFN-? producing CD4+ and CD8+ T cells in asthmatic compared with normal subjects. Further studies investigating T cells derived from the airways and investigating various stages within the disease process are required to further elucidate the importance of type 2 and type 1 T cell cytokine production in the pathogenesis of human allergic disease

Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells

Background: Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention. Objective: To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in-vitro. Methods: BEAS-2B cells were infected with major and minor RVs and the mRNA expression of IL-8, RANTES, MIP-1α, eotaxin, eotaxin-2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus-specificity of the observed reactions, cells were also exposed to inactivated RVs. Results: RV infection was able to up-regulate mRNA expression of IL-8, RANTES, MIP-1α, eotaxin and eotaxin-2, did not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL-8, RANTES and eotaxin, but not for MIP-1α. When RVs were inactivated cytokine up-regulation was almost completely lost. Conclusion: Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus-induced asthma exacerbations

Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells

Background Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention. Objective To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in-vitro. Methods BEAS-2B cells were infected with major and minor RVs and the mRNA expression of IL-8, RANTES, MIP-1?, eotaxin, eotaxin-2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus-specificity of the observed reactions, cells were also exposed to inactivated RVs. Results RV infection was able to up-regulate mRNA expression of IL-8, RANTES, MIP-1?, eotaxin and eotaxin-2, did not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL-8, RANTES and eotaxin, but not for MIP-1?. When RVs were inactivated cytokine up-regulation was almost completely lost. Conclusion Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus-induced asthma exacerbations

Respiratory virus induction of alpha-, beta- and lambda-interferons in bronchial epithelial cells and peripheral blood mononuclear cells.

BACKGROUND: Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-beta in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-lambdas in both BECs and bronchoalveolar lavage cells, is implicated in asthma exacerbation pathogenesis. Thus replacement of deficient interferon is a candidate new therapy for asthma exacerbations. Rhinoviruses and other respiratory viruses infect both BECs and macrophages, but their relative capacities for alpha-, beta- and lambda-interferon production are unknown. METHODS: To provide guidance regarding which interferon type is the best candidate for development for treatment/prevention of asthma exacerbations we investigated respiratory virus induction of alpha-, beta- and lambda-interferons in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Rhinovirus infection of BEAS-2B BECs induced interferon-alpha mRNA expression transiently at 8 h and interferon-beta later at 24 h while induction of interferon-lambda was strongly induced at both time points. At 24 h, interferon-alpha protein was not detected, interferon-beta was weakly induced while interferon-lambda was strongly induced. Similar patterns of mRNA induction were observed in primary BECs, in response to both rhinovirus and influenza A virus infection, though protein levels were below assay detection limits. In PBMCs interferon-alpha, interferon-beta and interferon-lambda mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-alpha>-beta>-lambda. Thus respiratory viruses induced expression of alpha-, beta- and lambda-interferons in BECs and PBMCs. In PBMCs interferon-alpha>-beta>-lambda while in BECs, interferon-lambda>-beta>-alpha. CONCLUSIONS: We conclude that interferon-lambdas are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferon-alphas in PBMCs, while interferon-beta is produced by both cell types