scholarly journals Human Leucocyte Antigen-G (HLA-G) and Its Murine Functional Homolog Qa2 in theTrypanosoma cruziInfection

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Fabrício C. Dias ◽  
Celso T. Mendes-Junior ◽  
Maria C. Silva ◽  
Fabrine S. M. Tristão ◽  
Renata Dellalibera-Joviliano ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Constitutive Expression ◽  
Tissue Expression ◽  
Functional Homolog ◽  
Susceptibility Factors ◽  
Mouse Tissues ◽  
Clinical Variants ◽  
Affected Mouse ◽  
Colonic Cells

Genetic susceptibility factors, parasite strain, and an adequate modulation of the immune system seem to be crucial for disease progression afterTrypanosoma cruziinfection. HLA-G and its murine functional homolog Qa2 have well-recognized immunomodulatory properties. We evaluated theHLA-G3′ untranslated region (3′UTR) polymorphic sites (associated with mRNA stability and target for microRNA binding) and HLA-G tissue expression (heart, colon, and esophagus) in patients presenting Chagas disease, stratified according to the major clinical variants. Further, we investigated the transcriptional levels of Qa2 and other pro- and anti-inflammatory genes in affected mouse tissues duringT. cruziexperimental acute and early chronic infection induced by the CL strain. Chagas disease patients exhibited differentialHLA-G3′UTR susceptibility allele/genotype/haplotype patterns, according to the major clinical variant (digestive/cardiac/mixed/indeterminate). HLA-G constitutive expression on cardiac muscle and colonic cells was decreased in Chagasic tissues; however, no difference was observed for Chagasic and non-Chagasic esophagus tissues. The transcriptional levels ofQa2and other anti and proinflammatory (CTLA-4, PDCD1, IL-10, INF-γ, andNOS-2) genes were induced only during the acuteT. cruziinfection in BALB/c and C57BL/6 mice. We present several lines of evidence indicating the role of immunomodulatory genes and molecules in human and experimentalT. cruziinfection.

scholarly journals Spi-1/PU.1 transgenic mice develop multistep erythroleukemias.

1996 ◽  
Vol 16 (5) ◽  
pp. 2453-2463 ◽  
Author(s):  
F Moreau-Gachelin ◽  
F Wendling ◽  
T Molina ◽  
N Denis ◽  
M Titeux ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Insertional Mutagenesis ◽  
Constitutive Expression ◽  
Transgenic Animals ◽  
Founder Line ◽  
Mouse Tissues ◽  
High Level

Insertional mutagenesis of the spi-1 gene is associated with the emergence of malignant proerythroblasts during Friend virus-induced acute erythroleukemia. To determine the role of spi-1/PU.1 in the genesis of leukemia, we generated spi-1 transgenic mice. In one founder line the transgene was overexpressed as an unexpected-size transcript in various mouse tissues. Homozygous transgenic animals gave rise to live-born offspring, but 50% of the animals developed a multistep erythroleukemia within 1.5 to 6 months of birth whereas the remainder survived without evidence of disease. At the onset of the disease, mice became severely anemic. Their hematopoietic tissues were massively invaded with nontumorigenic proerythroblasts that express a high level of Spi-1 protein. These transgenic proerythroblasts are partially blocked in differentiation and strictly dependent on erythropoietin for their proliferation both in vivo and in vitro. A complete but transient regression of the disease was observed after erythrocyte transfusion, suggesting that the constitutive expression of spi-1 is related to the block of the differentiation of erythroid precursors. At relapse, erythropoietin-independent malignant proerythroblasts arose. Growth factor autonomy could be partially explained by the autocrine secretion of erythropoietin; however, other genetic events appear to be necessary to confer the full malignant phenotype. These results reveal that overexpression of spi-1 is essential for malignant erythropoiesis and does not alter other hematopoietic lineages.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

scholarly journals AB0440 CLINICAL AND IMMUNOLOGICAL FEATURES OF THE SYSTEMIC SCLEROSIS-OVERLAP SYNDROMES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1248.2-1248
Author(s):  
O. Desinova ◽  
M. Starovoytova ◽  
L. P. Ananyeva ◽  
O. Koneva ◽  
L. Garzanova ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pathological Process ◽  
Point Of View ◽  
Joint Involvement ◽  
Laboratory Findings ◽  
Overlap Syndromes ◽  
Digital Ischemia ◽  
Immune Alterations ◽  
Clinical Variants

Background:Systemic Sclerosis (SSc) overlap syndromes (SSc with polymyositis / dermatomyositis (PM/DM), rheumatoid arthritis (RA), etc.) still remain a group of very heterogenous and not very well studied clinical variants of SSc that are characterized by certain clinical and immunological features.Objectives:Identify clinical and immunological features of the SSc-overlap syndromesMethods:80 pts with SSc-PM/DM and 35 pts with SSc-RA undergoing standard clinical examination and laboratory immunological evaluation.Results:ANA Hep2 was positive in 98% of SSc-PM/DM pts; a-Scl-70 was in 34%, a - PM-Scl and RF were in 20%. ACA (6%), a-RNP (9%), and a - Jo-1 (5%) were significantly less common. Correlation analysis showed significant prevalence of conduction abnormalities in pts with a-Scl-70- (p<0.03); PM-Scl was rarely associated with cardiac arrhythmia (p<0.02) and pericarditis (p<0.03), but there was an association between ACA and presence of digital ischemia (p<0.04). Three pts with limited skin had Scl-70 and PM-Scl antibodies, two of them manifested clinical features of DM. A-Jo-1 was found in 3 pts with a longstanding disease (14,10 and 7 years), and one of these pts was also positive for a-Scl-70. All pts had limited skin and two had interstitial lung disease with FVC values of 79% and 74.8%.ANA Hep2 was positive in 96% of SSc-RA pts; a-Scl-70 – in 28%, and a-RNP - in 30%. RF-positivity was in 72% of pts, and Anti-CCP - in 27%. Simultaneous Anti-CCP and a-Scl-70 was found in one case, and Anti-CCP - anti-RNP – in another, both were associated with low RF titers. All pts had early joint involvement which became prevailing in subsequent years, and onset of the disease between 30 and 36 years. There was a correlation between laboratory signs of inflammatory activity and immunological disorders: ESR and a-Scl-70 (p<0.03). Anti-CCP and a-Scl-70 co-positivity was a significantly less frequent phenomenon (p<0.04). There was a remarkable 28% proportion of a-Scl-70 cases in SSc-RA with limited cutaneous which is usually characterized by ACA-positivity.Conclusion:SSc-PM/DM and SSc-RA appear to be an active disease from the immunological point of view, confirming therefore an important role of immune alterations in disease progression. Laboratory findings display specific pathogenetic features of SSc-overlap syndromes; laboratory abnormalities can be used to measure the activity and specify characteristics of the pathological process.Disclosure of Interests:None declared

scholarly journals Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Marcela Hernández-Torres ◽  
Rogério Silva do Nascimento ◽  
Monica Cardozo Rebouças ◽  
Alexandra Cassado ◽  
Kely Catarine Matteucci ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
T Cell Response ◽  
No Production ◽  
Similar Reduction ◽  
Ifn Γ

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.

scholarly journals IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9

2013 ◽  
Vol 20 (5) ◽  
pp. 677-689 ◽  
Author(s):  
Holger H H Erb ◽  
Regina V Langlechner ◽  
Patrizia L Moser ◽  
Florian Handle ◽  
Tineke Casneuf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Tissue Expression ◽  
Type I ◽  
Regulatory Factor ◽  
Quantitative Real Time Pcr ◽  
Antiproliferative Effects ◽  
Protein Levels

Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.

Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2

Blood ◽  
2005 ◽  
Vol 105 (11) ◽  
pp. 4272-4281 ◽  
Author(s):  
Miranda Buitenhuis ◽  
Hanneke W. M. van Deutekom ◽  
Liesbeth P. Verhagen ◽  
Anders Castor ◽  
Sten Eirik W. Jacobsen ◽  
...  
Keyword(s):  
Critical Role ◽  
Ectopic Expression ◽  
Constitutive Expression ◽  
Retroviral Transduction ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Cd34 Cells ◽  
Final Maturation ◽  
Inhibitor Of Dna Binding

Abstract Inhibitor of DNA binding (Id) proteins function as inhibitors of members of the basic helix-loop-helix family of transcription factors and have been demonstrated to play an important role in regulating lymphopoiesis. However, the role of these proteins in regulation of myelopoiesis is currently unclear. In this study, we have investigated the role of Id1 and Id2 in the regulation of granulopoiesis. Id1 expression was initially up-regulated during early granulopoiesis, which was then followed by a decrease in expression during final maturation. In contrast, Id2 expression was up-regulated in terminally differentiated granulocytes. In order to determine whether Id expression plays a critical role in regulating granulopoiesis, Id1 and Id2 were ectopically expressed in CD34+ cells by retroviral transduction. Our experiments demonstrate that constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced. Constitutive Id2 expression accelerates final maturation of both eosinophils and neutrophils, whereas inhibition of Id2 expression blocks differentiation of both lineages. Transplantation of β2-microglobulin-/- nonobese diabetic severe combined immunodeficient (NOD/SCID) mice with CD34+ cells ectopically expressing Id1 resulted in enhanced neutrophil development, whereas ectopic expression of Id2 induced both eosinophil and neutrophil development. These data demonstrate that both Id1 and Id2 play a critical, although differential role in granulopoiesis.

scholarly journals Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

2021 ◽  
Vol 22 (14) ◽  
pp. 7374
Author(s):  
Changwu Wu ◽  
Yingjuan Duan ◽  
Siming Gong ◽  
Sonja Kallendrusch ◽  
Nikolas Schopow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Condensation ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Malignant Neoplasms ◽  
Nucleotide Exchange ◽  
Genome Database

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

scholarly journals Nod-Like Receptors in Host Defence and Disease at the Epidermal Barrier

2021 ◽  
Vol 22 (9) ◽  
pp. 4677
Author(s):  
Judit Danis ◽  
Mark Mellett
Keyword(s):  
Immune Response ◽  
Tissue Expression ◽  
Inflammasome Activation ◽  
Nucleotide Binding Domain ◽  
Microbial Infection ◽  
Epidermal Barrier ◽  
The Family ◽  
Bona Fide ◽  
Activation Antigen

The nucleotide-binding domain and leucine-rich-repeat-containing family (NLRs) (sometimes called the NOD-like receptors, though the family contains few bona fide receptors) are a superfamily of multidomain-containing proteins that detect cellular stress and microbial infection. They constitute a critical arm of the innate immune response, though their functions are not restricted to pathogen recognition and members engage in controlling inflammasome activation, antigen-presentation, transcriptional regulation, cell death and also embryogenesis. NLRs are found from basal metazoans to plants, to zebrafish, mice and humans though functions of individual members can vary from species to species. NLRs also display highly wide-ranging tissue expression. Here, we discuss the importance of NLRs to the immune response at the epidermal barrier and summarise the known role of individual family members in the pathogenesis of skin disease.

scholarly journals Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions

2018 ◽  
Vol 9 ◽  
Author(s):  
Ana Rosa Pérez ◽  
Alexandre Morrot ◽  
Vinicius Frias Carvalho ◽  
Juliana de Meis ◽  
Wilson Savino
Keyword(s):  
T Cell ◽  
Chagas Disease ◽  
T Cell Development ◽  
Cell Development
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