Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

Schistosomiasis is the most important human helminth infection in terms of morbidity and mortality. Although the efforts to develop a vaccine against this disease have experienced failures, a new generation of surface antigens revealed by proteomic studies changed this scenario. Our group has characterized the protein Sm29 described previously as one of the most exposed and expressed antigens in the outer tegument of Schistosoma mansoni. Studies in patients living in endemic areas for schistosomiasis revealed high levels of IgG1 and IgG3 anti-Sm29 in resistant individuals. In this study, confocal microscope analysis showed Sm29 present in the surface of lung-stage schistosoluma and adult worms. Recombinant Sm29, when used as vaccine candidate, induced high levels of protection in mice. This protection was associated with a typical Th1 immune response and reduction of worm burden, liver granulomas and in intestinal eggs. Further, microarray analysis of worms recovered from vaccinated mice showed significant down-regulation of several genes encoding previously characterized vaccine candidates and/or molecules exposed on the surface, suggesting an immune evasion strategy of schistosomes under immune attack. These results demonstrated that Sm29 as one of the important antigens with potential to compose a vaccine against schistosomiasis

Molecular Characterization of the Schistosoma mansoni Zinc Finger Protein SmZF1 as a Transcription Factor

Schistosomes are parasites that exhibit a complex life cycle during which they progress through many morphological and physiological transformations. These transformations are likely accompanied by alterations in gene expression, making genetic regulation important for parasite development. Here we describe a Schistosoma mansoni protein (SmZF1) that may act as a parasite transcription factor. These factors are key proteins for gene regulation. We have previously demonstrated that SmZF1 is able to bind DNA and that its mRNA is present at different stages during the parasite life cycle. In this study we aimed to define if this protein can function as a transcription factor in S. mansoni. SmZF1 was detected in the nucleus of adult male worms, cercariae and schistosomula cells. It was not, however, observed in female cells, suggesting it to be gender specific. We used mammalian cells expressing recombinant SmZF1 to analyze if SmZF1 protein is able to activate/repress gene transcription and demonstrated that it increased the expression of a reporter gene by two-fold. The results obtained confirm SmZF1 as a S. mansoni transcription factor

17β -estradiol Regulates and v-Ha-ras Transfection Constitutively Enhances MCF7 Breast Cancer Cell Interactions with Basement Membrane

The interaction of a line of human breast carcinoma cells (MCF7) with basement membrane components, particularly laminin, was altered by exposure of the cells to estrogen as well as by transfection of the cells with the v-Ha-ras oncogene. In both cases, the cells show a greater ability to attach to a laminin substrate, to migrate to laminin, to grow in the presence of a basement membrane matrix, and to cross barriers of reconstituted basement membrane. These responses were associated with an increase in the expression of laminin receptors. It is postulated that the increase in the invasive behavior of the cells treated with estrogen or transfected with v-Ha-ras is related to the increased number of laminin receptors and their interaction with laminin. Estrogen had no discernible effect on the v-Ha-ras transfected cells. It appears that in the MCF7 cells, the malignant phenotype is under hormonal control and that this control is bypassed after v-Ha-ras transfection

Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart.

In this study we investigated the effects of genetic deletion of the Angiotensin-(1-7) receptor Mas or the Angiotensin II receptor AT2 on the expression of specific extracellular matrix (ECM) proteins in atria, right ventricles and atrioventricular (AV) valves of neonatal and adult mice. Quantification of collagen types I, III and VI and fibronectin was performed using immunofluorescence-labeling and confocal microscopy. Picrosirius red staining was used for the histological assessment of the overall collagen distribution pattern. ECM proteins, metalloproteinases (MMP), ERK1/2 and p38 levels were quantified by western blot analysis. Gelatin zymography was used to evaluate the activity ofMMP-2 andMMP-9. We observed that the relative levels of collagen types I and III and fibronectin are significantly higher in both the right ventricle and AV valves of neonatal Mas?/? mouse hearts (e.g., collagen type I: 85.28?6.66 vs 43.50?4.41 arbitrary units in the right ventricles of Mas+/+ mice). Conversely, the level of collagen type VI was lower in the right ventricle and AV valves of Mas?/? mice. Adult Mas?/? mouse hearts presented similar patterns as observed in neonates. No significant differences in ECMprotein level were detected in atria. Likewise, no changes in ECM levels were observed in AT2 knockout mouse hearts. Although deletion of Mas induced a significant reduction in the level of the active form of MMP-2 in neonate hearts and a reduction of both MMP-2 and MMP-9 in adult Mas?/? mice, no significant differences were observed inMMP enzymatic activities when compared to controls. The levels of the active, phosphorylated forms of ERK1/2 and p38 were higher in hearts of both neonatal and adult Mas?/? mice. These observations suggest that Mas is involved in the selective expression of specific ECMproteins within both the ventricular myocardium and AV valves. The changes in the ECM profile may alter the connective tissue framework and contribute to the decreased cardiac performance observed in Mas?/? mice