Ena Ray Banerjee

Bio: Ena Ray Banerjee is an academic researcher from University of Calcutta. The author has contributed to research in topics: Stem cell & Embryonic stem cell. The author has an hindex of 12, co-authored 68 publications receiving 460 citations. Previous affiliations of Ena Ray Banerjee include University of Washington.

Human Embryonic Stem Cells Differentiated to Lung Lineage-Specific Cells Ameliorate Pulmonary Fibrosis in a Xenograft Transplant Mouse Model

Abstract: Background Our aim was to differentiate human (h) embryonic stem (ES) cells into lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI) and type II (AEII) cells and Clara cells] as the first step in the development of cell-based strategies to repair lung injury in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF). A heterogeneous population of non-ciliated lung lineage-specific cells was derived by a novel method of embryoid body (EB) differentiation. This differentiated human cell population was used to modulate the profibrotic phenotype in transplanted animals. Methodology and Principal Findings Omission or inclusion of one or more components in the differentiation medium skewed differentiation of H7 hES cells into varying proportions of AEI, AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/β-catenin/Creb-binding protein (CBP) transcription, changed marker expression of the differentiated ES cells from an AEII-like phenotype to a predominantly AEI-like phenotype. The differentiated cells were used in xenograft transplantation studies in bleomycin-treated Rag2γC−/− mice. Human cells were detected in lungs of the transplanted groups receiving differentiated ES cells treated with or without ICG-001. The increased lung collagen content found in bleomycin-treated mice receiving saline was significantly reduced by transplantation with the lung-lineage specific epithelial cells differentiated from ES cells. A significant increase in progenitor number was observed in the airways of bleomycin-treated mice after transplantation of differentiated hES cells. Conclusions This study indicates that ES cell-based therapy may be a powerful novel approach to ameliorate lung fibrosis.

Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma model

Abstract: Background (R)- and (S)-Enantiomers of albuterol likely exert differential effects in patients with asthma. The (R)-enantiomer binds to the β 2 -adrenergic receptor with greater affinity than the (S)-enantiomer and is responsible for albuterol's bronchodilating activity. (S)-Albuterol augments bronchospasm and has proinflammatory actions. Objective The study aim was to determine whether the (S)-enantiomer, in contrast to the (R)-enantiomer, has adverse effects on allergic airway inflammation and hyperresponsiveness in a mouse asthma model. Methods Mice sensitized to ovalbumin (OVA) intraperitoneally on days 0 and 14 were challenged with OVA intranasally on days 14, 25, and 35. On day 36, 24 hours after the final allergen challenge, the effect of the (R)- and (S)-enantiomers of albuterol (1 mg · kg −1 · d −1 administered by means of a miniosmotic pump from days 13-36) on airway inflammation and hyperreactivity was determined. Results In OVA-sensitized/OVA-challenged mice, (R)-albuterol significantly reduced the influx of eosinophils into the bronchoalveolar lavage fluid and airway tissue. (R)-Albuterol also significantly decreased airway goblet cell hyperplasia and mucus occlusion and levels of IL-4 in bronchoalveolar lavage fluid and OVA-specific IgE in plasma. Although (S)-albuterol significantly reduced airway eosinophil infiltration, goblet cell hyperplasia, and mucus occlusion, it increased airway edema and responsiveness to methacholine in OVA-sensitized/OVA-challenged mice. Allergen-induced airway edema and pulmonary mechanics were unaffected by (R)-albuterol. Conclusion Both (R)- and (S)-enantiomers of albuterol reduce airway eosinophil trafficking and mucus hypersecretion in a mouse model of asthma. However, (S)-albuterol increases allergen-induced airway edema and hyperresponsiveness. These adverse effects of the (S)-enantiomer on lung function might limit the clinical efficacy of racemic albuterol.

Role of free radicals in human inflammatory diseases

Abstract: The role of free radicals can be found in the inflammatory process which is a complex process resulting many human diseases. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. In recent years, there has been a great deal of attention to the field of free radical chemistry. Free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. The purpose of the present review is to mention the role of free radical formation in the most common inflammatory processes in animals. Continued oxidative stress can lead to chronic inflammation, which in turn could mediate the most chronic diseases including cancer, diabetes, cardiovascular, neurological, and pulmonary diseases. ROS and RNS are well recognized for playing role as deleterious species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. The detrimental effect of free radicals causing health damages is termed oxidative stress and nitrosative stress. Overproduction of ROS results in oxidative stress, a deleterious process that can damage cell structures, including lipids, proteins, and DNA.

Characterization of lung stem cell niches in a mouse model of bleomycin-induced fibrosis

Abstract: Introduction In lung fibrosis, alveolar epithelium degenerates progressively. The goal of regenerative medicine is to aid repair and regeneration of the lost tissues in parenchyma and airways for which mobilization of tissue-resident endogenous or bone marrow-derived exogenous stem cells niches is a critical step. We used a lung injury model in mice to identify and characterize functional lung stem cells to clarify how stem cell niches counteract this degenerative process.

α4 and β2 integrins have nonredundant roles for asthma development, but for optimal allergen sensitization only α4 is critical

Abstract: Objective Recruitment of effector cell subsets to inflammatory lung, together with airway resident cells responsive to secreted products, play pivotal roles in developing and maintaining asthma. Differential use of adhesion molecules dictates the recruitment patterns of specific cell subsets, yet a clear understanding of the distinctive adhesive molecular pathways guiding them to lung is lacking. To provide further insight into the role of α4β1/VCAM-1 pathway and to compare this to the role of β2 integrin in the development of acute asthma phenotype, we used genetically deficient mice, in contrast to previous studies with anti-functional antibodies yielding ambiguous results. Methods Allergen-dependent airway inflammation and hyperresponsiveness was induced in conditional α4 Δ/Δ , VCAM-1 −/− , and β2 −/− mice. Cytology, immunocytochemistry, cytokine and immunoglobulin measurements, and cell type accumulation in lung, BAL fluid, plasma, and hemopoietic tissues were carried out. Results Asthma phenotype was totally abrogated in α4- or β2-deficient mice. Adoptive transfer of sensitized α4 Δ/Δ CD4 + cells into challenged normal mice failed to induce asthma, whereas α4 +/+ CD4 + cells were able to induce asthma in challenged α4 Δ/Δ mice. Parallel studies with β2 −/− or VCAM-1 −/− mice uncovered novel mechanistic insights in primary sensitization and into redundant or unique functional roles of these adhesion pathways in allergic asthma. Conclusions The lack of α4 integrin not only impedes the migration of all white cell subsets to lung and airways, but also prevents upregulation of vascular cell adhesion molecule-1 (VCAM-1) in inflamed lung vasculature and, unlike β2, attenuates optimal sensitization and ovalbumin-specific IgE production in vivo. As VCAM-1 deficiency did not protect mice from asthma, interactions of α4β1 + or α4β7 + cells with other ligands are suggested.

Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces

Abstract: The regulatory T (Treg) cells restrain immune responses through suppressor-function elaboration that is dependent upon expression of the transcription factor Foxp3. Despite a critical role for Treg cells in maintaining lympho-myeloid homeostasis, it remains unclear whether a single mechanism or multiple mechanisms of Treg cell-mediated suppression are operating in vivo and how redundant such mechanisms might be. Here we addressed these questions by examining the role of the immunomodulatory cytokine IL-10 in Treg cell-mediated suppression. Analyses of mice in which the Treg cell-specific ablation of a conditional IL-10 allele was induced by Cre recombinase knocked into the Foxp3 gene locus showed that although IL-10 production by Treg cells was not required for the control of systemic autoimmunity, it was essential for keeping immune responses in check at environmental interfaces such as the colon and lungs. Our study suggests that Treg cells utilize multiple means to limit immune responses. Furthermore, these mechanisms are likely to be nonredundant, in that a distinct suppressor mechanism most likely plays a prominent and identifiable role at a particular tissue and inflammatory setting.

Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement

Abstract: Significance: Oxidative stress, an excess of reactive oxygen species (ROS) production versus consumption, may be involved in the pathogenesis of different diseases. The only known enzymes solely dedicated to ROS generation are nicotinamide adenine dinucleotide phosphate (NADPH) oxidases with their catalytic subunits (NOX). After the clinical failure of most antioxidant trials, NOX inhibitors are the most promising therapeutic option for diseases associated with oxidative stress. Recent Advances: Historical NADPH oxidase inhibitors, apocynin and diphenylene iodonium, are un-specific and not isoform selective. Novel NOX inhibitors stemming from rational drug discovery approaches, for example, GKT137831, ML171, and VAS2870, show improved specificity for NADPH oxidases and moderate NOX isoform selectivity. Along with NOX2 docking sequence (NOX2ds)-tat, a peptide-based inhibitor, the use of these novel small molecules in animal models has provided preliminary in vivo evidence for a pathophysiological ...

Total Cranberry Extract vs. its Phytochemical Constituents: Antiproliferative and Synergistic Effects against Human Tumor Cell Lines

Abstract: Cranberries (Vaccinium macrocarpon Ait.) are an excellent dietary source of phytochemicals that include flavonol glycosides, anthocyanins, proanthocyanidins (condensed tannins), and organic and phenolic acids. Using C-18 and Sephadex Lipophilic LH-20 column chromatography, HPLC and tandem LC-ES/MS, we have analyzed, quantified and separated total cranberry extract (TCE) into fractions enriched in sugars, organic acids, total polyphenols, proanthocyanidins and anthocyanins (39.4, 30.0, 10.6, 5.5, 1.2% composition, respectively). Using a luminescent ATP cell viability assay, the antiproliferative effects of TCE (200 g/mL) vs. all fractions were evaluated against human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, RWPE-2, 22Rv1) cancer cell lines. The total polyphenol fraction was the most active fraction against all cell lines with 96.1 and 95% inhibition of KB and CAL27 oral cancer cells, respectively. For the colon cancer cells, the antiproliferative activity of this fraction was greatest against HCT116 (92.1%) than HT-29 (61.1%), SW480 (60%) and SW620 (63%). TCE and all fractions, showed 50% antiproliferative activity against prostate cancer cells with total polyphenols being the most active fraction (RWPE-1, 95%; RWPE-2, 95%; 22Rv1, 99.6%). Cranberry sugars (78.8 g/mL) did not inhibit the proliferation of any cancer cell lines. The enhanced antiproliferative activity of total polyphenols compared to TCE and its individual phytochemicals suggests synergistic or additive antiproliferative interactions of the anthocyanins, proanthocyanidins and flavonol glycosides within the cranberry extract.

Book review: Experimental techniques in plant disease epidemiology, J. Kranz & J. Rotem (eds.). Springer-Verlag Berlin, 1989, 299 pp.

Abstract: Various textbooks have been written on the epidemiology of plant diseases. Most of them present theory of epidemiology, thus giving a description of epidemiological principles. Some of these are of a general nature, whereas others concentrate on specialized subjects, but there are no books on experimental techniques in epidemiology. This omission has been recognized and rectified by Kranz and Rotem. As mentioned in their preface they intended, by editing and publishing the book, 'to help in the development of a methodology able to provide a choice of adequate methods widely acceptable amongst epidemiologists for varying applications and objectives'. For this purpose, they invited 27 distinguished plant pathologists, a number of them from Kranz's 'stable', to participate, and to provide information from their own rich experience. There are 20 chapters spread over four sections. Section I (General techniques), deals with techniques and approaches used in experiments in the field and under controlled conditions. Advantages and disadvantages of such experiments and the relations between them are explained. In Section II (.Measurements and their analysis) disease assessment, crop development and estimation of spore production, dispersal, survival and infectiousness are treated. The analysis of spatial patterns of soil-borne pathogens {s discussed in a separate chapter, for soil-borne diseases have to be approached differently. This section is concluded with two chapters on the monitoring and analysis of environmental factors. Section III (Special topics) is a collection of items, such as the analysis of the effects of control measures, fungicide resistance, virulence in pathogen populations, components in yield loss, development of forecasters, aphid-borne epidemiology, quantitative nematology, geophytopathology and long-distance dispersal. As the editors explain, these are 'not necessarily connected with each other, but all dealing with definite objectives in epidemiological experimentation'. The reasoning for the addition of these topics to the contents is clear. Most are worth treatment, and each has specialized techniques and approaches. The reasoning for collecting them all together under 'Special topics' is a little unsatisfactory. A rather simple rearrangement and naming of the subjects could separate them into a couple of better defined chapters, which would have made the contents more accessible to the eager user. Section IV (The synopsis of experimental restilts) gives the reader a look into the methods in comparative epidemiology, and into the development and use of simulation models for root and foliar diseases. The limitations, necessarily imposed upon the authors, to prevent the publication of an unwieldy and ever more expensive handbook lead to the question whether the editors 'bit more than they could chew'. Especially the chapters on modeling and simulation suffer under these limitations. Most authors have achieved a fine work, though readers, familiar with the authors' publications, can 'taste' a bit of subject.ivity in the choice and approach of techniques and methods by some of them. The book might be a useful addition to the library of all those involved in experimental work in epidemiology, but particularly those called 'novices in epidemiology' in the preface. The editors may have had undergraduates and young postgraduates in mind, but this work might be useful for other epidemiologists too. It is a pity that the high price will hinder young scientists from purchasing the book, particularly those in developing countries.