0000000000495252
AUTHOR
Francesca Magno
The balance of HSPs expression during pregnancy: the role of placenta
New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity.
In recent years, human mesenchymal stem cells (MSC) have been extensively studied. Their key characteristics of long-term self-renewal and a capacity to differentiate into diverse mature tissues favour their use in regenerative medicine applications. Stem cells can be found in embryonic and extra-embryonic tissues as well as in adult organs. Several reports indicate that cells of Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells, expressing markers of bone marrow mesenchymal stem cells (BM-MSC), and giving rise to different cellular types of both connective and nervous tissues. Wharton's jelly mesenchymal stem cells (WJ-MSC) express …
ROLE OF SMADS IN REMODELLING OF THE LARGE AIRWAYS IN PATIENTS WITH COPD.
Oxidative stress upregulates eNOS and myeloperoxidase (MPO) immunoexpression in hydrogen peroxide (H2O2) exposed HUVEC cells.
CCL5(RANTES) inhibits TGFbeta1 induced collagen production in human bronchial epithelial cells by action of Smad protein
Airway epithelial cells modulate bronchial remodelling in COPD and asthma. TGF-β1 up-regulation was observed in the bronchial epithelial cells of asthmatics and COPD patients. TGF-β is involved in airways remodelling mainly acting via the Smad pathway. Increased CCL5 was also observed in bronchi of patients with severe COPD. We investigated the effects of TGF-β1 on collagen type I, Smad 3-4 and 7 expression and the effects of CCL5 on TGF-β1-induced collagen production in human bronchial epithelial cells (16HBE).Cells were treated with 10ng/ml of TGF-β1, 10ng/ml of CCL5 and 10ng/ml of both TGF-β1 and CCL5 for 0,3 and 24 hours.TGF-b1 increased Smad3,Smad4 and collagen type I(p=0.0472, p=0.043…
Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts
Abstract Background Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD.…
Extended characterization of human umbilical cord matrix mesenchymal stem cells: expression of novel markers, immunoregulatory molecules, and differentiating potency.
HSP60 and HSP10 downregulation predicts bronchial epithelial carcingenesis.
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.
BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …
Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD
BACKGROUND: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. OBJECTIVES: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. METHODS: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chai…
Role of oxidative and nitrosative stress biomarkers in chronic heart failure
In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pu…
Cigarette smoke affects heat-shock proteins in human lung fibroblasts: a proteomic study and identification of three expressed HSP10 variants differentially affected by the stressor
Isolation, characterization, differentiative properties of human mesenchymal stem cells isolated from the sub-endocardial layer of post-infarct chronic heart failure-affected patients
Mesenchymal stem cells (MSC) are pluripotent cells which reside in several adult organs, including heart, even if heart regeneration in vivo is still a poorly comprised phenomenon. Contrasting literature reports suggest that several efforts should be made to better characterize resident or migrating MSC populations (for both markers expression and immunogenic potential) prior to their effective use for regenerative medicine applications in heart diseases. We developed a new protocol to obtain human sub-endocardial MSC (HSE-MSC) from post-infarct hearts explanted from chronic heart failure (CHF) patients undergoing heart transplantation. We characterized HSE-MSC by immunocytochemistry (ICC) …
Increased nitrotyrosine plasma levels in relation to systemic markers of inflammation and myeloperoxidase in chronic heart failure
The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H(2)O(2), total NO, nitrite (NO(2)(-)), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFalpha) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (p<0.05), NYHA I (p<0.03) and controls (p<0.02), whereas NO(2)(-) and total NO …
Oxidative Stress Upregulates eNOS and Myeloperoxidase (MPO) immunoexpression in hydrogen peroxide (H202) exposed HUVEC cells
CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome.
AIMS: CD1a is a molecule belonging to the highly conserved group of CD1 proteins. Its expression in dendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently, the development of a successful antitumour response. The aim was to investigate the presence of CD1a+ cells in both primary tumours and lymph nodes (LN) of a series of 35 invasive ductal carcinomas by both immunohistochemistry and reverse transcription-polymerase chain reaction. METHODS AND RESULTS: CD1a antigen was more expressed in N0 than N1 breast cancer (P < 0.0001) in both primary lesions and LN metastases and correlated positively and significantly with oestrogen (ER) (P =…
Human Wharton's jelly-derived mesenchymal stem cells express several immunomodulatory molecules both in their naïve state and hepatocyte-like differentiated progeny: prospects for their use in liver diseases
Wharton’s jelly (WJ), the main constituent of umbilical cord, is a reliable source of mesenchymal stem cells (MSC). WJ-MSC show unique ability in crossing lineage borders. As other extraembryonic mesenchymal populations (placenta and amnionderived cells), WJ-MSC express several immunomodulatory molecules, essential during the initial phases of human development. Indeed, our recent work pointed out the expression of non-classical HLA molecules as HLA-G in such cells, together with a favorable combination of B7 costimulators. Very few data in literature suggest that some of the immune features of the naïve cells are maintained after performing differentiation. The aim of this work was extendi…
Increased nitrotyrosine immunoreactivity in bronchial biopsies from patients with severe COPD
Hsp10 beyond mitochondria: novel locations predict as yet undescribed roles
CD1a expression in primary breast cancer and lymph nodes: correlation with clinicopathological parameters.
Role of Smads in respiratory disease pathogenesis
Transforming Growth Factor beta (TGFβ) cytokine plays an important role in normal pulmonary morphogenesis and function as well as in the pathogenesis of lung diseases. The principal signaling pathway downstream to activate TGFβ is the Smad pathway. Even though many studies have focused on Smads’ structural features and pathway, less is known about the possible relationship between protein and mRNA expression of Smads and lung diseases. This review will focus on Smads and sum up what is know about their role in some respiratory diseases: COPD,asthma end fibrosis
Contribution of bronchial biopsies in the evaluation of pathogenesis and progression of COPD.
This review summarizes and discusses the lung pathology of COPD patients emphasising on inflammatory cell phenotypes and mechanisms which prevail in different clinical conditions. In bronchial biopsies a series of events takes place during the progression of the disease from mild to severe. T-lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lungs of healthy smokers and patients with mild/moderate COPD. This T-cell activation seems to be sustained by CD4+, CD8+ cells and macrophages expressing transcription factors and Tc1 cytokines such as NF-kB, STAT4 and IFNγ. In contrast, severe disease is characterized by lymphocytes producing greater amo…
CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome
Aims: CD1a is a molecule belonging to the highlyconserved group of CD1 proteins. Its expression indendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently,the development of a successful antitumour response.The aim was to investigate the presence of CD1a+ cellsin both primary tumours and lymph nodes (LN) ofa series of 35 invasive ductal carcinomas by bothimmunohistochemistry and reverse transcription-poly-merase chain reaction.Methods and results: CD1a antigen was more expressedin N0 than N1 breast cancer (P < 0.0001) in bothprimary lesions and LN metastases and correlatedpositively and significantly with oestrogen (ER) (P =0.0025) and…
Epithelial overexpression of Interleukin-8 in bronchial biopsies from patients with COPD
Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure.
Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 mic…
Extending the usefulness of extraembryonic mesenchymal stem cellsin regenerative medicine: expression of novel markers, immunoregulatory molecules, and novel differentiation capacities.
Mesenchymal stem cells (MSC) are considered promising tools in regenerative medicine applications. Even if they are already applied clinically, their extended characterization is being increasingly viewed as a needed feature, in order to avoid contrasting results when translating “in vitro” experiments to “in vivo” approaches. We recently demonstrated in human MSC isolated from the umbilical cord matrix (HEMSC) the expression of novel markers indicative of their stemness, as well as differentiative and immune properties [1]. HEMSC were cultured and subject to multiple molecular and morphological analyses to determine the expression of markers of interest. Undifferentiated HEMSC expressed im…
Two isoelectric variants of HSP10 are down-regulated by cigarette smoke exposure in airway cells: A Proteomic study
Cigarette smoke exposure affects expression and extracellular activity levels of gelatinase A and B in airway epithelial cells
Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers
The presence of multipotent cells in several adult and embryo-related tissues opened new paths for their use in regenerative medicine. Extraembryonic tissues such as umbilical cord are considered a promising source of stem cells, potentially useful in therapy. The characterization of cells from the umbilical cord matrix (Wharton''s Jelly) and amniotic membrane revealed the presence of a population of mesenchymal-like cells, sharing a set of core-markers expressed by "mesenchymal stem cells". Several reports enlightened the differentiation capabilities of these cells, even if at times the lack of an extensive characterization of surface markers and immune co-stimulators expression revealed h…
Distribution of mitochondrial chaperonins in lung cells
Pro-and anti-fibrotic molecule balance in the bronchial mucosa of stable COPD patients
Background: The mechanisms of inducing fibrotic events and remodeling in the airways of COPD are incompletely studied. Objectives: To investigate the expression of cytokines involved in the pro- and anti-fibrotic events in stable COPD. Methods: Expression of CTGF, TGFβ1-2-3, TGFβRI, TGFβRII, LTBP-1, TRAP-1, BAMBI, PP2Cα, Smad2-3-6-7, pSmad2, pSmad3, pro-collagen-I and collagen-I was measured in the bronchial mucosa using immunohistochemistry and RT-qPCR. Results: TGFβ1 was increased in the epithelium and TGFβ3 in the submucosa of healthy smokers and mild/moderate COPD compared to healthy non-smokers. In all smokers and patients with COPD TGFβ3+ cells in the submucosa correlated significantl…
Cigarette smoke affects heat-shock proteins in human lung fibroblasts: a proteomic study and identification of three expressed HSP10 variants differentially affected by stressor.
A novel isolation technique and extended characte-rization of mesenchymal stem cells from human umbilical cord matrix: disclosing new potentials for regenerative medicine applications.
In vitro and in vivo detection of end-products of MPO-driven oxidative and nitrosative stress in human endocardial endothelial cells from patients affected by chronic heart failure
Th17-related cytokine expression is increased in the bronchial mucosa of stable COPD patients
Background: There is an increased number of activated Tl lymphocytes in the bronchial mucosa of stable COPD patients but are absent studies on Th17 cells and their effector cytokines.Objectives: To investigate the expression of retinoic orphan receptor(ROR)C2, interleukin(IL)-17A,IL-17F,IL-21,IL-22 and IL-23 in bronchial biopsies from patients with stable COPD of different severity(stage 2 to 4)compared with age-matched control subject(smokers with normal lung function and lifelong non-smokers).Methods: The expression of RORC2,IL-17A,IL-17F,IL-21,IL-22 and IL-23 was measured in the bronchial mucosa using immunohistochemistry and/or real time quantitative polymerase chain reaction. Results: …
Isolation and characterization of human extraembryonal mesoderm mesenchymal stem cells from umbilical cord
TGFbeta signaling: roles of Smads
CIGARETTE SMOKE AFFECTS HEAT-SHOCK PROTEINS IN HUMAN LUNG FIBROBLASTS: A PROTEOMIC STUDY AND IDENTIFICATION OF THREE EXPRESSED HSP10 VARIANTS DIFFERENTIALLY AFFECTS BY STRESSOR.
Effect of a pathogenic stressor on human HSP10.
Oxidative stress-driven expression of myeloperoxidase in endothelial cells results in accumulation of markers of oxidative and nitrosative stress in vitro and in vivo
Endothelial cells (ECs), are able to manage with higher concentrations of ROS as well as reactive nitrogen species, respect to the other cell types. The unbalance between oxidizing species and antioxidant cellular defences has been implicated in the pathogenesis of cardiovascular diseases. While the role of MPO in the oxidative burst is well established, the effects of this enzyme on endothelial biology have only recently come to light. MPO can interact with endothelial –derived NO causing its depletion and favouring its conversion to nitrogen dioxide radical, a compound responsible of protein nitration generating 3-nitrotyrosine. Moreover, MPO is the only enzyme capable to form hypoclorous…
Telomerase activity and telomeric states in cell proliferative and differentiative mechanisms.
Telomeres are DNA-protein complexes playing an important role in the maintenance of genome integrity. Telomerase is the enzyme acting as a template for addition of new telomeric repeats; this addition is essential for those cellular populations that have proliferative and differentiative potential. Telomerase and associated proteins are essential in response to DNA damage. Moreover, telomere-associated proteins as TRF2 are involved in all signalling transduction pathway which drive cellular proliferation and differentiation. In somatic cells, shortening of telomeres contributes to the onset of senescence or apoptosis; tissues which require cellular renewal express telomerase activity in ord…
Role of TGF-b1 in type I collagen production in bronchial epithelial cells: effects on Smad7 inhibitory role?
Airway epithelial cells play an important role in inflammatory, apoptotic and remodelling process associate with fibrosis and COPD. Transforming growth factor 1 (TGF-b1) is involved in airways remodelling by Smads signalling pathway. We investigated the role of TGF-b1 on type I collagen production and Smads (Smad 2-3-4-and 7) expression in bronchial epithelial cells (16HBE). Cells were treated with 1ng/ml and 10ng/ml of TGF-b1 for 0, 3 and 24 hours. With low dose of TGF-b1 we observed no significant variation on Smad2 mRNA expression for both times but a significant increased of Smad7 mRNA expression at 3h (p=0.0043) and a significant reduction of Smad3, Smad4 and Smad7 mRNA expression at 2…
Effect of a pathogenetic stressor on human Hsp10.
Hydrogen peroxide in endothelium: multifaceted roles in cellular stress and signalling.
Cigarette smoke exposure downregulates two isoelectric variants of human HSP10 in airway epithelial cells: A Proteomic study
Aumentata adesione neutrofilica nelle biopsie bronchiali di pazienti con BPCO grave.
Increased neutrophil adhesion in bronchial biopsies from patients with severe COPD.
T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients.
Summary There are increased numbers of activated T lymphocytes in the bronchial mucosa of stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17 (Th17) cells release interleukin (IL)-17 as their effector cytokine under the control of IL-22 and IL-23. Furthermore, Th17 numbers are increased in some chronic inflammatory conditions. To investigate the expression of interleukin (IL)-17A, IL-17F, IL-21, IL-22 and IL-23 and of retinoic orphan receptor RORC2, a marker of Th17 cells, in bronchial biopsies from patients with stable COPD of different severity compared with age-matched control subjects. The expression of IL-17A, IL-17F, IL-21, IL-22, IL-23 and RORC2 was measure…
Pathogenesis and progression of COPD: contribution of bronchial biopsies.
Role of endothelial cell stress in the pathogenesis of chronic heart failure.
Endothelial cells are key modulators of diverse physiological processes, and their impaired function is a cause of numerous cardiovascular diseases. Under physiologic condition, the reactive oxygen and nitrogen mediators in endothelia lead to the signal propagation of the initial stimulus, by forming molecules with a longer half-life like hydrogen peroxide. Hydrogen peroxide is the focus of growing attention in endothelial biology, and consequently the enzymes involved in its generation and clearance are viewed as novel mediators of great importance. In particular, among peroxidases, myeloperoxidase is recognized as a key enzyme, capable of impairing intracellular NO reservoirs as well as p…