The role of CD14 gene promoter polymorphism in tuberculosis susceptibility

BackgroundCD14 is expressed principally by cells of monocyte/macrophage lineage and plays a pivotal role in the innate immunity to intracellular infections. Recent research findings have revealed an association between the CD14 gene promoter polymorphism and several major infectious diseases.ObjectiveThe aim of the present study was to investigate the association between the CD14-159C/T polymorphism and tuberculosis in a Turkish population.MethodsFor this purpose, 88 consecutive patients with tuberculosis (63 pulmonary, 25 extrapulmonary) and 116 control subjects were enrolled into a prospective study. We determined CD14-159 genotypes by polymerase chain reaction - restriction fragment length polymorphism analysis and also measured serum concentrations of soluble CD14 (sCD14) by using a quantitative sandwich enzyme immunoassay technique.ResultsThere was no significant difference in terms of genotype distribution between patients with tuberculosis (CC 18.2%, CT 48.9%, TT 33.0%) and controls (CC 12.9%, CT 50.9%, TT 36.2%) or between patients with pulmonary and extrapulmonary tuberculosis. Serum levels of sCD14 were significantly increased in patients with active tuberculosis compared to those with inactive tuberculosis and healthy controls (p<0.001). However, levels of sCD14 were not associated with any genotypes of CD14-159.ConclusionThe genotyping findings of the present study do not support a role for the CD14-159C/T polymorphism in the development of tuberculosis, at least in the geographical region of central Anatolia. Significantly elevated serum sCD14 levels in patients with active disease reflect the importance of the mononuclear phagocytic system activation in tuberculosis

The effects of an insertion in the 5 ' UTR of the AMCase on gene expression and pulmonary functions

Cataloged from PDF version of article.Background: Studies regarding the physiological role of acidic mammalian chitinase (AMCase) and the effects of its genetic variants on asthma have produced conflicting results. Objectives: We aimed to determine the genetic variants in the AMCase gene that could regulate the gene expression and thus influence disease severity. Methods: Genetic variants of the AMCase gene were determined by sequencing of asthmatics and healthy controls in up to -1 kb in the promoter region and exon 1 and 2. In an association study, a population of asthmatic (n = 504) and healthy Turkish children (n = 188) were genotyped for the observed SNPs. A replication study was performed in a North American adult population of patients with mild (n = 317) and severe (n = 145) asthma. The functional properties of the insertion were determined by promoter reporter assay, electromobility shift assay and transcription factor ELISA experiments. Results: Of the identified SNPs, only a ten base pair insertion (CAATCTAGGC) in the 5'UTR region of exon 2 was significantly associated with lower FEV(1) (beta = -14.63 SE = 6.241, P = 0.019) in Turkish children with asthma. However, in the adult population, the same insertion showed a trend toward higher FEV(1). The insertion was shown to have enhancer activity and the mutant probe possessing the insertion had higher binding affinity for the nuclear extracts. Conclusion: Our study shows that a ten base pair insertion in the 5'UTR region of AMCase gene may modify gene expression and thus may affect the severity of asthma. However, its effects appear to be different in different populations. (C) 2011 Elsevier Ltd. All rights reserved

Antiangiogenic response after 70% hepatectomy and its relationship with hepatic regeneration and angiogenesis in rats

Background: The aim of this study was to evaluate the antiangiogenic response and its relation to regeneration and angiogenesis after 70% hepatectomy in a rat model. Methods: Sixty-four Wistar albino rats were included in the study. Animals were allocated into 8 groups (n = 8). After a 70% hepatectomy, liver regeneration, angiogenesis, and antiangiogenic response were evaluated in the remnant liver on days 0, 1, 2, 3, 5, 7, 10, and 14. Regeneration and angiogenesis were determined with immunoreactivity to proliferating cell nuclear antigen and vascular endothelial growth factor. Antiangiogenic response was evaluated by detecting collagen 18 m RNA with reverse transcriptase polymerase chain reaction. Results: We showed that liver regeneration peaked at day 1, whereas angiogenesis in the periportal and perisinusoidal areas reached their peak values on days 3 and 7, respectively. Both regeneration and angiogenic activity around perisinusoidal hepatocytes returned to basal activity on the day 10. Antiangiogenic response first appeared on day 5, reached a peak on day 10, and returned to basal values on day 14. Conclusion: Collagen18 mRNA expression is present in the normal liver during the regenerative process. We suggest that the stimulus that causes the cessation of regeneration process may come from hepatocytes, and collagen 18 produced by hepatocytes may modulate this event by inhibiting the angiogenesis. © 2010 Mosby, Inc. All rights reserved

NanoDCFH-DA: a silica based nanostructured fluorogenic probe for the detection of reactive oxygene species

A biocompatible fluorescent nanoprobe for the detection of reactive oxygen species in biological systems has been designed, synthesized and characterized, circumventing some of the limitations of the molecular probe diacetyl 2',7'-dihidrochlorodihydrofluorescein (DCFH-DA). It has been synthesized the nanoparticulate forme of DCFH-DA by convalently attaching the widely used fluorescent probe DCFH-DA to a mesoporous silica nanoparticle though a linker, The reactivity of nanoDCFH-DA has been tested toward several reactive oxygen species. In addition, it has been proven to slow down DCFH-DA reaction with molecular oxygen and it hampers from interactions with proteins. As a final piece of evidence, in vitro studies showed that the nanoprobe is internalized HeLa cancer cells, thus being capable of detecting intracellularly generated reactive oxygen species. To sum up, it can be stated that nanoDCFH-DA overcomes two major problems of free DCFH-DA, namely oxidation of the probe by air and interaction with proteins in biological systems. This 'nano' approach has thus proven useful to extend the utility of an existing and valuable fluorescent probe to complex biological systems

Triclosan Disrupts SKN-1/Nrf2- Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment