Evaluation of P2X7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of Chagas disease

2017 ◽  
Vol 104 ◽  
pp. 32-38 ◽  
Author(s):  
Viviane do Carmo Gonçalves Souza ◽  
Joabel Tonellotto dos Santos ◽  
Fernanda Licker Cabral ◽  
Fernanda Barbisan ◽  
Maria Isabel Azevedo ◽  
...  
Keyword(s):  
Chagas Disease ◽  
P2x7 Receptor ◽  
Receptor Expression ◽  
Immune Profile ◽  
Peripheral Lymphocytes ◽  
Indeterminate Form

scholarly journals Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy

2019 ◽  
Vol 20 (16) ◽  
pp. 4064 ◽  
Author(s):  
Carolina Kymie Vasques Nonaka ◽  
Carolina Thé Macêdo ◽  
Bruno Raphael Ribeiro Cavalcante ◽  
Adriano Costa de Alcântara ◽  
Daniela Nascimento Silva ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Pharmacological Therapy ◽  
Functional Class ◽  
Diagnostic Methods ◽  
Individual Risk ◽  
Indeterminate Form ◽  
Potential Biomarkers

Chagas disease (CD) affects approximately 6–7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.

scholarly journals Echocardiographic Study of the Coronary Sinus in the Indeterminate Form of Chagas Disease

2018 ◽  
Vol 51 (6) ◽  
pp. 827-830
Author(s):  
Glauco Andre Machado ◽  
Dalton Alexandre dos Anjos ◽  
Flávia de Freitas Rodrigues ◽  
Renata Fockink dos Anjos ◽  
Marcelo Barbosa Melo Luckemeyer ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Coronary Sinus ◽  
Echocardiographic Study ◽  
Indeterminate Form

Abstract B208: Reduction in P2X7 receptor expression is a marker of resistance to ATP treatment in human cervical carcinoma cell line.

2013 ◽  
Author(s):  
Paola de Andrade Mello ◽  
Eduardo Cremonese Filippi-Chiela ◽  
Jessica Nascimento ◽  
Franciele Cristina Kipper ◽  
Aline Beckenkamp ◽  
...  
Keyword(s):  
Cell Line ◽  
Cervical Carcinoma ◽  
P2x7 Receptor ◽  
Carcinoma Cell ◽  
Receptor Expression ◽  
Carcinoma Cell Line ◽  
Human Cervical Carcinoma ◽  
Cervical Carcinoma Cell Line

Regulation of P2X7 receptor expression and function in the brain

2019 ◽  
Vol 151 ◽  
pp. 153-163 ◽  
Author(s):  
Eva M. Jimenez-Mateos ◽  
Jonathon Smith ◽  
Annette Nicke ◽  
Tobias Engel
Keyword(s):  
P2x7 Receptor ◽  
Receptor Expression ◽  
And Function ◽  
The Brain

scholarly journals T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Mauricio Llaguno ◽  
Marcos Vinicius da Silva ◽  
Lara Rocha Batista ◽  
Djalma Alexandre Alves da Silva ◽  
Rodrigo Cunha de Sousa ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Chronic Phase ◽  
Interleukin 10 ◽  
T Helper ◽  
T Helper 1 ◽  
Cardiac Damage ◽  
Disease Treatment ◽  
Indeterminate Form ◽  
Ifn Γ

ABSTRACT The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25− and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.

scholarly journals The indeterminate form of human chronic Chagas' disease: a clinical epidemological review

1989 ◽  
Vol 22 (3) ◽  
pp. 147-156 ◽  
Author(s):  
João Carlos Pinto Dias
Keyword(s):  
Natural History ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Clinical Findings ◽  
X Rays ◽  
Classical Concept ◽  
Positive Serology ◽  
Indeterminate Form ◽  
History Of ◽  
Chronic Chagas Disease

Data on the epidemiology and the natural history of the indeterminate form of human chronic Chagas' disease (IFCCD) are discussed, revealing its great importance in endemic areas of Brazil. The work shows that IFCCD presents a gradual and very slow course, causing a benign picture in the studied patients. Evolution patterns, prognostic and anatomopathological features are also discussed. For practical purposes, the classical concept of IFCCD proved to be simple, operational and consistent, It is defined by the absence of symptoms and clinical findings in chronic infected patients with positive serology and/or parasitological examinations for Trypanosoma cruzi coupled with normal electrocardiographic and radiological exams (heart, oesophagus and colon X-Rays). If a patient is submitted to more rigorous and sophisticated tests, these can reveal some alterations, generally small ones and unable to interfere with the prognosis of the infection. It is suggested that research lines specially related to the evolution ary factors and immunological involvement during this phase be adopted.

Functional expression of purinergic P2X7 receptors in pregnant rat myometrium

2010 ◽  
Vol 298 (4) ◽  
pp. R1117-R1124 ◽  
Author(s):  
Hiroshi Miyoshi ◽  
Kaoru Yamaoka ◽  
Satoshi Urabe ◽  
Miho Kodama ◽  
Yoshiki Kudo
Keyword(s):  
P2x7 Receptor ◽  
Uterine Contraction ◽  
Extracellular Atp ◽  
Receptor Expression ◽  
P2x Receptor ◽  
Receptor Subtype ◽  
P2x7 Receptors ◽  
Pregnant Rat ◽  
Myometrial Cells ◽  
Induced Currents

ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 μM-1 mM and induced currents with an EC50 of 74 μM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K+ > Cs+ > Li+ > Na+. They were activated by P2X receptor agonists, with their effectiveness ranked as 2′,3′- O-(4-benzoylbenzoyl)-ATP >> ATP > αβ-methylene-ATP > 2-methylthio ATP ≥ UTP ≥ GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg2+ (IC50 = 0.26 mM). Clinically, administering extracellular Mg2+ is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg2+ inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.

scholarly journals P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx

2003 ◽  
Vol 374 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Jan AMSTRUP ◽  
Ivana NOVAK
Keyword(s):  
P2x7 Receptor ◽  
Fluorescent Protein ◽  
Expression System ◽  
Receptor Expression ◽  
Nucleotide Receptors ◽  
P2x7 Receptors ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Extracellular Signal

P2X7 nucleotide receptors modulate a spectrum of cellular events in various cells including epithelia, such as exocrine pancreas. Although the pharmacology and channel properties of the P2X7 receptors have been studied intensively, signal transduction pathways are relatively unknown. In this study we applied a heterologous expression system of rat P2X7 receptors in HEK-293 cells. We followed the receptor expression and function using the enhanced green fluorescent protein (EGFP) tag, activation of intracellular proteins and increases in cellular Ca2+. EGFP-P2X7 receptors localized to the plasma membrane, clusters within the membrane and intracellularly. Stimulation of P2X7 receptors in HEK-293 cells led to an activation of extracellular signal-regulated kinases ERK1 and ERK2 and this activation was seen after just 1 min of stimulation with ATP. Using C- and N-terminal P2X7-receptor mutants we show that the N-terminus is important in activation of ERKs, whereas deletion of the last 230 amino acids in the C-terminus did not effect ERK activation. On the other hand, Ca2+ entry was impaired in C-terminal but not in N-terminal mutants. In cell suspensions prepared from rat pancreas we show that P2X7 receptors also activate ERK1 and ERK2, indicating that these signalling pathways are also turned on in native epithelium.

Modulation of P2X7 receptor expression in macrophages from mineral oil-injected mice

Immunobiology ◽  
2008 ◽  
Vol 213 (6) ◽  
pp. 481-492 ◽  
Author(s):  
Camila Marques da Silva ◽  
Luciana Miranda Rodrigues ◽  
Andressa Passos da Silva Gomes ◽  
Marcio Mantuano Barradas ◽  
Flávia Sarmento Vieira ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Mineral Oil ◽  
Receptor Expression

scholarly journals Early impairment of myocardial deformation assessed by regional speckle-tracking echocardiography in the indeterminate form of Chagas disease without fibrosis detected by cardiac magnetic resonance

2020 ◽  
Vol 14 (11) ◽  
pp. e0008795
Author(s):  
Minna Moreira Dias Romano ◽  
Henrique Turin Moreira ◽  
José Antônio Marin-Neto ◽  
Priscila Elias Baccelli ◽  
Fawaz Alenezi ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Myocardial Fibrosis ◽  
Chagas Disease ◽  
Speckle Tracking ◽  
Longitudinal Strain ◽  
Speckle Tracking Echocardiography ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Indeterminate Form

Chagas disease (CD) will account for 200,000 cardiovascular deaths worldwide over the next 5 years. Early detection of chronic Chagas cardiomyopathy (CCC) is a challenge. We aimed to test if speckle-tracking echocardiography (STE) can detect incipient myocardial damage in CD. METHODS: Among 325 individuals with positive serological tests, 25 (age 55±12yrs) were selected to compose the group with indeterminate form of Chagas disease (IFCD), based on stringent criteria of being asymptomatic and with normal EKG/X-ray studies. This group was compared with a group of 20 patients with CCC (55±11yrs) and a group of 20 non-infected matched control (NC) subjects (48±10yrs). CD patients and NC were submitted to STE and CD patients were submitted to cardiac magnetic resonance (CMR) with late gadolinium administration to detect cardiac fibrosis by the late enhancement technique. Global longitudinal strain (GLS), circumferential (GCS) and radial strain (GRS) were defined as the average of segments measured from three apical view (GLS) and short axis views (GRS and GCS). Regional left ventricular (LV) longitudinal strain (Reg LS) was measured from each of the 17 segments. Twist was measured as systolic peak difference between basal and apical rotation and indexed to LV length to express torsion. RESULTS: STE global indices (GLS, GCS, twist and torsion) were reduced in CCC vs NC (GLS: -14±6.3% vs -19.3±1.6%, p = 0.001; GCS: -13.6±5.2% vs -17.3 ±2.8%; p = 0.008; twist: 8±7° vs 14±7°, p = 0.01 and torsion: 0.96±1°/cm vs 1.9±1°/cm, p = 0.005), but showed no differences in IFCD vs NC. RegLS was reduced in IFCD vs NC in four LV segments: basal-inferior (-16.3±3.3% vs -18.6±2.2%, p = 0.013), basal inferoseptal (-13.1±3.4 vs -15.2±2.7, p = 0.019), mid-inferoseptal (-17.7±3.2 vs -19.4±2, p = 0.032) and mid-inferolateral (-15.2±3.5 vs -17.8±2.8, p = 0.014). These abnormalities in RegLS occurred in the absence of myocardial fibrosis detectable with CMR in nearly 92% of subjects with IFCD, while myocardial fibrosis was present in 65% with CCC. CONCLUSION: RegLS detects early regional impairment of myocardial strain that is independent from fibrosis in IFCD subjects.

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