High dose vitamin D empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma.

Allergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)VitD (VitD3), can improve efficacy of AIT.

Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma.

Allergic asthma is characterized by airway hyperresponsiveness, remodeling, and reversible airway obstruction. This is associated with an eosinophilic inflammation of the airways, caused by inhaled allergens such as house dust mite or grass pollen. The inhaled allergens trigger a type-2 inflammatory response with the involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high immunoglobulin E (IgE) antibody production by B cells and mucus production by airway epithelial cells.

Cellular senescence impairs the reversibility of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown.

1,25(OH)VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model.

Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy.

Age-determined severity of anti-myeloperoxidase autoantibody-mediated glomerulonephritis in mice.

Background: Anti-neutrophil cytoplasmic antibody associated vasculitis (AAV) is a typical disease of the elderly. In AAV, there is an age-specific increase in disease incidence with age being a predictor of disease outcome. In this study, we aimed to determine the contribution of age to the development of AAV employing a mouse model of anti-myeloperoxidase (MPO) antibody-mediated glomerulonephritis.

Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice.

High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice.

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

Purpose: The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney.

Methods: We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs.

Protease-activated receptor-2 activation contributes to house dust mite-induced IgE responses in mice.

Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium, thereby potentially inducing allergic sensitization at the expense of inhalation tolerance. We hypothesized that the proteolytic activity of allergens may play an important factor in the allergenicity to house dust mite and is essential to overcome airway tolerance.

Flush at room temperature followed by storage on ice creates the best lung graft preservation in rats.

Current clinical lung preservation techniques have not eliminated ischaemia-reperfusion (I/R) injury, despite many improvements. The optimal combination of flush and storage temperatures remain unclear in lung preservation. This is the first study to investigate a range of temperatures with 24-h inflated storage using consistent state-of-the-art preservation techniques.

Development and in-vivo characterization of supramolecular hydrogels for intrarenal drug delivery.

Intrarenal drug delivery from a hydrogel carrier implanted under the kidney capsule is an innovative way to induce kidney tissue regeneration and/or prevent kidney inflammation or fibrosis. We report here on the development of supramolecular hydrogels for this application. We have synthesized two types of supramolecular hydrogelators by connecting the hydrogen bonding moieties to poly(ethylene glycols) in two different ways in order to obtain hydrogels with different physico-chemical properties.

Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo.

Objective: To determine whether inhibition of p38 mitogen-activated protein kinase (p38MAPK) reduces the pathogenicity of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in vitro and in vivo.

Methods: The effects of the p38MAPK-specific inhibitor AR-447 were studied in vitro using neutrophil respiratory burst and degranulation assays, and in lipopolysaccharide (LPS)-stimulated human glomerular endothelial cells. In vivo, p38MAPK inhibition was investigated in a mouse anti-myeloperoxidase (MPO) IgG/LPS glomerulonephritis model.

IgG glycan hydrolysis attenuates ANCA-mediated glomerulonephritis.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor-mediated activation of leukocytes and complement. Here, we investigated whether IgG hydrolysis by the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN.

Efficacy of a new pulmonary cyclosporine a powder formulation for prevention of transplant rejection in rats.

Background: The aim of this pilot study was to determine the pharmacokinetics of cyclosporine A powder for inhalation (iCsA) and its rejection prevention efficacy in an experimental lung transplantation model in rats.

Methods: Single-dose pharmacokinetics (10 mg/kg) of pulmonary and orally administered cyclosporine A was determined in whole blood and in lung and kidney tissue. The efficacy of iCsA (2.

Ciclosporin does not influence bone marrow-derived cell differentiation to myofibroblasts early after renal ischemia/reperfusion.

Background: Ischemia/reperfusion injury (IRI) is a risk factor for the development of interstitial fibrosis. Previously we had shown that after renal IRI, bone marrow-derived cells (BMDC) can differentiate to interstitial myofibroblasts. Here we hypothesized that the immunosuppressant ciclosporin A (CsA), known for its profibrotic side effect, promotes myofibroblast differentiation of BMDC in the postischemic kidney.

Cryoinjury: a model of myocardial regeneration.

Introduction: Although traditionally adult cardiomyocytes are thought to be unable to divide, recent observations provide evidence for cardiomyocyte proliferation after myocardial injury. Myocardial cryoinjury has been shown to be followed by neovascularization. We hypothesize that, in addition to neovascularization, cardiomyocyte proliferation after myocardial cryoinjury contributes to regeneration.

Site-specific inhibition of glomerulonephritis progression by targeted delivery of dexamethasone to glomerular endothelium.

Glomerulonephritis represents a group of renal diseases with glomerular inflammation as a common pathologic finding. Because of the underlying immunologic character of these disorders, they are frequently treated with glucocorticoids and cytotoxic immunosuppressive agents. Although effective, use of these compounds has limitations as a result of toxicity and systemic side effects.

Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice.

Macrophages have been suggested to be beneficial for myocardial wound healing. We investigated the role of macrophages in myocardial wound healing by inhibition of macrophage infiltration after myocardial injury. We used a murine cryoinjury model to induce left ventricular damage.

Stem cell-related cardiac gene expression early after murine myocardial infarction.

Objective: Clinical experimental stem cell therapy after myocardial infarction appears feasible, but its use has preceded the understanding of the working mechanism. The ischemic recipient cardiac environment is determinative for the attraction and subsequent fate of stem cells. Here, we studied expression levels of genes that are anticipated to be essential for adequate stem cell-based cardiac repair at various time-points during the 1 month period following myocardial infarction (MI).

Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats.

Bone marrow-derived cells (BMDC) have been proposed to exert beneficial effects after renal ischemia/reperfusion injury (IRI) by engraftment in the tubular epithelium. However, BMDC can give rise to myofibroblasts and may contribute to fibrosis. BMDC contribution to the renal interstitial myofibroblast population in relation to fibrotic changes after IRI in rats was investigated.

The correlation between difference in foreign body reaction between implant locations and cytokine and MMP expression.

The foreign body reaction (FBR) differs between subcutaneously and supra-epicardially implanted materials. We hypothesize that this is a result of differences in cytokine, chemokine and matrix metalloproteinase (MMP) dynamics. Therefore we applied collagen disks subcutaneously and on the epicardium in mice and analyzed the FBR from day 1 to 21.

Increased inflammatory response and neovascularization in reperfused vs. non-reperfused murine myocardial infarction.

Introduction: Fundamental knowledge of the inflammatory response after myocardial infarction (MI) is indispensable for intervention toward cardiac regeneration. Although reperfusion is preferred as clinical therapy, for basic research, also permanent ligation MI models are widely used.

Methods: In this report, we pathohistologically compared the kinetics of the inflammatory and angiogenic response after MI induced by permanent ligation or ligation followed by reperfusion of the left anterior descending coronary artery in mice.

Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats.

Background: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned in view of their relatively low frequency.

The enzymatic degradation of scaffolds and their replacement by vascularized extracellular matrix in the murine myocardium.

Replacement of injured myocardium by cell-based degradable scaffolds is a novel approach to regenerate myocardium. Understanding the foreign body reaction (FBR) induced by the scaffold is requisite to predict unwanted site effects or implant failure. We evaluated the FBR against a biodegradable scaffold applied on injured myocardium in mice.