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#33198383   2020/11/12 To Up

A Novel HGF/SF Receptor (MET) Agonist Transiently Delays the Disease Progression in an Amyotrophic Lateral Sclerosis Mouse Model by Promoting Neuronal Survival and Dampening the Immune Dysregulation.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with no effective treatment. The Hepatocyte Growth Factor/Scatter Factor (HGF/SF), through its receptor MET, is one of the most potent survival-promoting factors for motor neurons (MN) and is known as a modulator of immune cell function. We recently developed a novel recombinant MET agonist optimized for therapy, designated K1K1. K1K1 was ten times more potent than HGF/SF in preventing MN loss in an in vitro model of ALS. Treatments with K1K1 delayed the onset of muscular impairment and reduced MN loss and skeletal muscle denervation of superoxide dismutase 1 G93A (SOD1G93A) mice. This effect was associated with increased levels of phospho-extracellular signal-related kinase (pERK) in the spinal cord and sciatic nerves and the activation of non-myelinating Schwann cells. Moreover, reduced activated microglia and astroglia, lower T cells infiltration and increased interleukin 4 (IL4) levels were found in the lumbar spinal cord of K1K1 treated mice. K1K1 treatment also prevented the infiltration of T cells in skeletal muscle of SOD1G93A mice. All these protective effects were lost on long-term treatment suggesting a mechanism of drug tolerance. These data provide a rational justification for further exploring the long-term loss of K1K1 efficacy in the perspective of providing a potential treatment for ALS.
Antonio Vallarola, Massimo Tortarolo, Roberta De Gioia, Luisa Iamele, Hugo de Jonge, Giovanni de Nola, Enrica Bovio, Laura Pasetto, Valentina Bonetto, Mattia Freschi, Caterina Bendotti, Ermanno Gherardi

2971 related Products with: A Novel HGF/SF Receptor (MET) Agonist Transiently Delays the Disease Progression in an Amyotrophic Lateral Sclerosis Mouse Model by Promoting Neuronal Survival and Dampening the Immune Dysregulation.

100 μg500 100ug100 μg100ug

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#33193307   2020/10/23 To Up

Crosstalk Between Dermal Fibroblasts and Dendritic Cells During Dengue Virus Infection.

Dengue virus infection (DENV-2) is transmitted by infected mosquitoes the skin, where many dermal and epidermal cells are potentially susceptible to infection. Most of the cells in an area of infection will establish an antiviral microenvironment to control viral replication. Although cumulative studies report permissive DENV-2 infection in dendritic cells, keratinocytes, and fibroblasts, among other cells also infected, little information is available regarding cell-to-cell crosstalk and the effect of this on the outcome of the infection. Therefore, our study focused on understanding the contribution of fibroblast and dendritic cell crosstalk to the control or promotion of dengue. Our results suggest that dendritic cells promote an antiviral state over fibroblasts by enhancing the production of type I interferon, but not proinflammatory cytokines. Infected and non-infected fibroblasts promoted partial dendritic cell maturation, and the fibroblast-matured cells were less permissive to infection and showed enhanced type I interferon production. We also observed that the soluble mediators produced by non-infected or Poly (I:C) transfected fibroblasts induced allogenic T cell proliferation, but mediators produced by DENV-2 infected fibroblasts inhibited this phenomenon. Additionally, the effects of fibroblast soluble mediators on CD14 monocytes were analyzed to assess whether they affected the differentiation of monocyte derived dendritic cells (moDC). Our data showed that mediators produced by infected fibroblasts induced variable levels of monocyte differentiation into dendritic cells, even in the presence of recombinant GM-CSF and IL-4. Cells with dendritic cell-like morphology appeared in the culture; however, flow cytometry analysis showed that the mediators did not fully downregulate CD14 nor did they upregulate CD1a. Our data revealed that fibroblast-dendritic cell crosstalk promoted an antiviral response mediated manly by type I interferons over fibroblasts. Furthermore, the maturation of dendritic cells and T cell proliferation were promoted, which was inhibited by DENV-2-induced mediators. Together, our results suggest that activation of the adaptive immune response is influenced by the crosstalk of skin resident cells and the intensity of innate immune responses established in the microenvironment of the infected skin.
Alfredo E Montes-Gómez, Julio García-Cordero, Edith Marcial-Juárez, Gaurav Shrivastava, Giovani Visoso-Carvajal, Francisco J Juárez-Delgado, Leopoldo Flores-Romo, Ma Carmen Sanchez-Torres, Leopoldo Santos-Argumedo, José Bustos-Arriaga, Leticia Cedillo-Barrón

1683 related Products with: Crosstalk Between Dermal Fibroblasts and Dendritic Cells During Dengue Virus Infection.

5001000 1.00 flask25100200 1.00 flask1.00 flask1000100μg500 100

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#33154744   2020/10/14 To Up

Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines.

There is mounting evidence that galectin-3 is a prognostic and diagnostic biomarker associated with diverse diseases and conditions, including cancer, cardiovascular disease, autoimmunity, wound healing, allergic disease, and chronic inflammation in general. Yet, whether and exactly how galectin-3 may participate in the pathogenesis of these diseases remains poorly understood. Recently, we have linked the expression of galectin-3 on the A549 epithelial cell line -an adenocarcinoma, to the activation of human basophils for the release of histamine and secretion of IL-4 and IL-13. These responses proved dependent on cell-to-cell contact, basophil expression of IgE, were inhibited by n-acetyllactosamine, and were ablated when basophils were co-cultured with A549 clones lacking galectin-3 expression. While recombinant galectin-3 failed to activate basophils when in solution, microspheres expressing this lectin did so by mimicking the responses seen when using A549 cells. Given the IgE dependency of the basophil responses, and the fact that galectin-3 is long known to bind this immunoglobulin, we hypothesize that a similar mode of activation extends to other IgE-bearing cells. To investigate this possibility, we tested epithelial cell-associated galectin-3 for its capacity to activate human dendritic cells, including the plasmacytoid and myeloid subtypes as well as monocytes, all of which bind IgE. Indeed, results indicate that epithelial cell-associated galectin-3 activated these cells for robust production of TNF-α and IL-6 and up-regulated the expression of activation markers found on dendritic cells. Moreover, many of the same parameters previously observed for basophils applied to the findings herein, including evidence that matrix-bound galectin-3 (whether on epithelial cells or microspheres) facilitates this mode of activation. In contrast, IgE expression was dispensable for these galectin-3-dependent cytokine responses, implying that this lectin activates dendritic cells (and monocytes) by binding to a glycoprotein other than this immunoglobulin. Overall, these findings further demonstrate how galectin-3 mediates immune cell activation, providing novel insight into how this lectin may promote chronic inflammation underlying the pathogenesis of many diseases.
John T Schroeder, Abiodun A Adeosun, Anja P Bieneman

2968 related Products with: Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines.

1.00 mg 100ul96 wells (1 kit)25 One 96-Well Microplate Ki1 kit(96 Wells) 100ulOne 96-Well Microplate Ki1 kit(96 Wells)96T

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#32880064   2020/09/02 To Up

Construction of genetically modified Lactococcus lactis that produces bioactive anti-interleukin-4 single-chain fragment variable.

Interleukin 4 (IL-4) is a cytokine that induces T-cell differentiation and the production of antibodies from B cells, and plays a crucial role in the allergic response. Therefore, development of a therapeutic approach against IL-4 signaling is expected to prevent or control Th2-related allergic diseases. IL-4 single-chain fragment variable (scFv), which is a recombinant protein consisting of the Fv region of an IL-4 antibody connected to a flexible peptide linker, is expected to be an inhibitor of IL-4 signaling. In this study, recombinant IL-4 scFv was produced by genetically modified lactic acid bacteria (gmLAB); this system is gaining attention as a type of microbial therapeutics. Recombinant gene expression was confirmed with western blotting, and the IL-4 recognition ability of IL-4 scFv produced by gmLAB was examined with an enzyme-linked immunosorbent assay. The macrophage cell line, Raw264.7, and peritoneal macrophages isolated from C57BL/6 mice were employed for an in vitro IL-4 signaling inhibition assay. IL-4 stimulation increased the mRNA expression of arginase-1, a biomarker of IL-4 signaling in macrophages, but arginase-1 expression was suppressed by IL-4 scFv produced by gmLAB, indicating that IL-4 scFv has IL-4 signaling inhibitory activity. gmLAB that produces bioactive IL-4 scFv that was constructed in this study could be an attractive approach for treating allergic disorders.
Fu Namai, Suguru Shigemori, Tasuku Ogita, Takashi Sato, Takeshi Shimosato

1433 related Products with: Construction of genetically modified Lactococcus lactis that produces bioactive anti-interleukin-4 single-chain fragment variable.

1 mg100.00 ug100ug Lyophilized0.02ml2 mg1 mg1 mg1.00 mg100ug Lyophilized50 1 ml1 mL

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#32194549   2020/02/28 To Up

Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection.

Memory B-cell dysfunctions and inefficient antibody response suggest germinal center (GC) impairments during HIV/SIV infection with possible contribution of overproduced B-cell activating factor (BAFF). To address this question, we compared proportions and functions of various B-cell subsets and follicular helper T-cells (T) in untreated (Placebo) and BR3-Fc treated (Treated) SIV-infected macaques. From day 2 post-infection (dpi), Treated macaques received one weekly injection of BR3-Fc molecule, a soluble BAFF antagonist, for 4 weeks. Whereas, the kinetics of CD4 T-cell loss and plasma viral loads were comparable in both groups, BAFF blockade delayed the peak of inflammatory cytokines (CXCL10, IFNα), impaired the renewal of plasmacytoid dendritic cells and fostered the decline of plasma CXCL13 titers after 14 dpi. In Treated macaques, proportions of total and naïve B-cells were reduced in blood and spleen whereas SIV-induced loss of marginal zone (MZ) B-cells was only accentuated in blood and terminal ileum. Proportions of spleen GC B-cells and T were similar in both groups, with CD8 T-cells and rare Foxp3 being present in spleen GC. Regardless of treatment, sorted T produced similar levels of IL21, CXCL13, and IFNγ but no IL2, IL4, or BAFF and exhibited similar capacities to support IgG production by autologous or heterologous B-cells. Consistently, most T were negative for BAFF-R and TACI. Higher proportions of resting and atypical (CD21) memory B-cells were present in Treated macaques compared to Placebo. In both groups, we found higher levels of BAFF-R expression on MZ and resting memory B-cells but low levels on atypical memory B-cells. TACI was present on 20-30% of MZ, resting and atypical memory B-cells in Placebo macaques. BAFF blockade decreased TACI expression on these B-cell subsets as well as titers of SIV-specific and vaccine-specific antibodies arguing for BAFF being mandatory for plasma cell survival. Irrespective of treatment, GC B-cells expressed BAFF-R at low level and were negative for TACI. In addition to key information on spleen BAFF-R and TACI expression, our data argue for BAFF contributing to the GC reaction in terminal ileum but being dispensable for the generation of atypical memory B-cells and GC reaction in spleen during T-dependent response against SIV.
Gwenoline Borhis, Maria Trovato, Hany M Ibrahim, Stephane Isnard, Roger Le Grand, Nathalie Bosquet, Yolande Richard

2128 related Products with: Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection.

100 mg1000.1 mg15ml100ul5ug1.00 flask1000 Reactions 25 MG1.5x10(6) cells5 reactions100.00 ug

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#32086822   2020/03/10 To Up

IL-1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice.

Early-life wheezing-associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV infection of 6-day-old immature mice causes mucous metaplasia and airway hyperresponsiveness which is associated with the expansion of IL-13-producing type 2 innate lymphoid cells (ILC2s) and dependent on IL-25 and IL-33. We examined regulation of this asthma-like phenotype by IL-1β.
Mingyuan Han, Tomoko Ishikawa, Jennifer R Bermick, Charu Rajput, Jing Lei, Adam M Goldsmith, Caitlin R Jarman, Julie Lee, J Kelley Bentley, Marc B Hershenson

1623 related Products with: IL-1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice.

96T96T10 100 μg1 kit96 tests10250ul4 Membranes/Box5mg4 Membranes/Box2000 Units

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#31863534   2020/01/02 To Up

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Bullous pemphigoid, mucous membrane pemphigoid, and pemphigus vulgaris are different cutaneous autoimmune blistering diseases, with complex pathogenic mechanisms. In all of them, a type-2 response is thought to have a central role. Interleukin 4 and Interleukin 13 are crucial cytokines in type-2 response. Treatment of these conditions is often challenging. Dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα, has the potential to inhibit both IL-4 and IL-13. We propose IL-4Rα as a theoretical drug target for cutaneous autoimmune bullous diseases.
Roberto Russo, Emanuele Cozzani, Giulia Gasparini, Aurora Parodi

1179 related Products with: Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

500 100ug Lyophilized96T100ug Lyophilized96 wells (1 kit)100ug Lyophilized600 Tests / Kit2.5 g100ug Lyophilized

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#31825972   2019/12/11 To Up

IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection.

Ebolavirus (EBOV) outbreaks, while sporadic, cause tremendous morbidity and mortality. No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials. A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen. As macrophages are an important cell population targeted during virus replication, we explore the effect of cytokine polarization on macrophage infection.
Kai J Rogers, Bethany Brunton, Laura Mallinger, Dana Bohan, Kristina M Sevcik, Jing Chen, Natalie Ruggio, Wendy Maury

2929 related Products with: IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection.

200 1 mg200 200ug 1L96 Tests n100 µg50ug100 100ug Lyophilized10050 mg

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