TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells

BACKGROUND AND AIMS Tumour necrosis factor α (TNF-α) represents a classical proinflammatory cytokine and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti- TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity. METHODS AND RESULTS Mice with genetic deletion of TNF-α (Tnf+/- and Tnf-/-) and littermate controls (Tnf+/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCR-M) models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide (αMyHC) showed reduced myocarditis incidence but the susceptible animals developed extensive inflammation in the heart. In the TCR-M model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-α as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-α produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+/- and Tnf-/- mice. Indeed, antigen-activated Tnf-/- Teff cells showed prolonged long-term survival and TNF-α cytokine-induced cell death of heart-reactive Teff. CONCLUSIONS TNF-α signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-α protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-α therapy in heart failure patients and open perspectives for T cell-targeted approaches

TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells

BACKGROUND AND AIMS Tumour necrosis factor α (TNF-α) represents a classical proinflammatory cytokine and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti- TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity. METHODS AND RESULTS Mice with genetic deletion of TNF-α (Tnf+/- and Tnf-/-) and littermate controls (Tnf+/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCR-M) models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide (αMyHC) showed reduced myocarditis incidence but the susceptible animals developed extensive inflammation in the heart. In the TCR-M model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-α as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-α produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+/- and Tnf-/- mice. Indeed, antigen-activated Tnf-/- Teff cells showed prolonged long-term survival and TNF-α cytokine-induced cell death of heart-reactive Teff. CONCLUSIONS TNF-α signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-α protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-α therapy in heart failure patients and open perspectives for T cell-targeted approaches

Heme oxygenase-1 is required for angiogenic function of bone marrow-derived progenitor cells : role in therapeutic revascularization

Aims: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that can be down-regulated in diabetes. Its importance for mature endothelium has been described, but its role in proangiogenic progenitors is not well known. We investigated the effect of HO-1 on the angiogenic potential of bone marrow-derived cells (BMDCs) and on blood flow recovery in ischemic muscle of diabetic mice. Results: Lack of HO-1 decreased the number of endothelial progenitor cells (Lin−CD45−cKit-Sca-1+VEGFR-2+) in murine bone marrow, and inhibited the angiogenic potential of cultured BMDCs, affecting their survival under oxidative stress, proliferation, migration, formation of capillaries, and paracrine proangiogenic potential. Transcriptome analysis of HO-1−/− BMDCs revealed the attenuated up-regulation of proangiogenic genes in response to hypoxia. Heterozygous HO-1+/− diabetic mice subjected to hind limb ischemia exhibited reduced local expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), stromal cell-derived factor 1 (SDF-1), VEGFR-1, VEGFR-2, and CXCR-4. This was accompanied by impaired revascularization of ischemic muscle, despite a strong mobilization of bone marrow-derived proangiogenic progenitors (Sca-1+CXCR-4+) into peripheral blood. Blood flow recovery could be rescued by local injections of conditioned media harvested from BMDCs, but not by an injection of cultured BMDCs. Innovation: This is the first report showing that HO-1 haploinsufficiency impairs tissue revascularization in diabetes and that proangiogenic in situ response, not progenitor cell mobilization, is important for blood flow recovery. Conclusions: HO-1 is necessary for a proper proangiogenic function of BMDCs. A low level of HO-1 in hyperglycemic mice decreases restoration of perfusion in ischemic muscle, which can be rescued by a local injection of conditioned media from cultured BMDCs

Voltammetric Detection of Glucose—The Electrochemical Behavior of the Copper Oxide Materials with Well-Defined Facets

Cu2O nanomaterials with well-defined facets and uniform size were synthesized by a wet-chemical method. Regardless of the additive composition, powders crystallize mostly in cuprite form. To compare their electrochemical behavior, the obtained materials were deposited on carbon glassy electrodes. The response to glucose from the materials with different exposed facets was recorded with a delay at the anodic curve. The chronoamperometric analyses (AMP) exhibited a lower signal in contrast to the cyclic voltammetry data (CV), indicating that the number of active sites involved in glucose oxidation processes resulting from the structure of the material is insufficient. For samples with dominant (100) or (111) planes, a typical characteristic was observed, however, with an additional peak at the anodic curve. The location of the peaks is approximately the same and no significant differences from the AMP and CV analysis were observed. The sample enclosed by the (111) facets exhibited higher activity; however, as a result of the redox reaction with glucose molecules, the surface state is changing. Cu2O materials enclosed by (100) planes exhibited optimal sensitivity as well as a large detective range. Samples with differential facet exposition present various current–potential profiles, as the effect of binder–particle interaction with Nafion

Nanostruktury na bazie TiO2 dla zastosowań fotoelektrochemicznych /

Promotor: Marta Radecka.Niepublikowana praca doktorska.Praca doktorska. Akademia Górniczo-Hutnicza im. St. Staszica w Krakowie. Wydział Inżynierii Materiałowej i Ceramiki, 2015.Bibliogr. s. 127-141.Nanostruktury, klasyfikacja nanostruktur, wybrane nanostruktury, nanostruktury typu 0D, nanostruktury typu 3D, fotokataliza heterogeniczna, procesy fotokatalityczne z wykorzystaniem półprzewodników, rozkład fotokatalityczny oranżu metylowego oraz błękitu metylowego, właściwości fotoelektrochemiczne półprzewodników, dwutlenek tytanu TiO2, własności fizykochemiczne TiO2, struktura krystaliczna, struktura elektronowa i właściwości optyczne, heterostruktury półprzewodnikowe na bazieTiO2, zastosowanie nanomateriałów na bazieTiO2, metody otrzymywania nanomateriałów, nanostruktury 0D, nanoproszki, nanostruktury typu core-shell, nanostruktury typu hollow shperes, nanostruktury 3D, nanostruktury typu flower_like, metodyka badań, struktura krystaliczna, właściwości mikrostrukturalne, właściwości optyczne, właściwości fotoelektrochemiczne, właściwości fotokatalityczne, właściwości elektryczne i elektrochemiczne, wyniki badań własnych, nanostruktury 0D, nanoproszki, core-shell, hollow spheres, nanostruktury 3D typu flower_like, nanostruktury TiO2, nanostruktury TiO2/CdS, nanostruktury TiO2/SnO

Transition-Metal-Based Compounds for Electrochemical Energy Conversion Processes

The era of ever-growing worldwide energy requirements demands the development of new methods of energy conversion, where the design of novel materials and the improvement of the efficiency of existing ones are of great importance [...

From Adsorbent to Photocatalyst: The Sensitization Effect of SnO2 Surface towards Dye Photodecomposition

Semiconductor photocatalysis is considered one of the most promising technologies for water purification from toxic organic dyes. However, to reliably evaluate the possibility of using a given material as a photocatalyst, it is crucial to investigate not only the photocatalytic activity but also its affinity towards various dyes and reusability. In this work, we studied the adsorptive/photocatalytic properties of hollow-spherical raspberry-like SnO2 and its SnO2/SnS2 heterostructures that were obtained via a chemical conversion method using three different concentrations of a sulfide precursor (thioacetamide). The adsorptive/photocatalytic properties of the samples towards cationic rhodamine B (RhB) and anionic indigo carmine (IC) were analyzed using uncommon wall zeta potential measurements, hydrodynamic diameter studies, and adsorption/photodecomposition tests. Moreover, after conducting cyclic experiments, we investigated the (micro)structural changes of the reused photocatalysts by scanning electron microscopy and Fourier-transform infrared spectroscopy. The obtained results revealed that the sensitization of SnO2 resulted not only in the significantly enhanced photocatalytic performance of the heterostructures, but also completely changed their affinity towards dyes. Furthermore, despite the seemingly best photocatalytic performance, the sample with the highest SnS2 content was unstable due to its (micro)structure. This work demonstrates that dye adsorption/desorption processes may overlap the results of cyclic photodecomposition kinetics