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Eosinophil - epithelial cell interaction augments cysteinyl leukotrienes synthesis

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Eosinophils accumulation in the airways and sustained eosinophil-derived cysteinyl leukotrienes production represent key elements of the inflammatory response seen in asthma.However,it is not known whether activated epithelial cells influence cysteinyl leukotrienes production by eosinophils from healthy valunteers.The aim of the present study was therefore to analyse the effects of interactions between non-atopic eosinophils and epithelial cells on cysteinyl leukotrienes production in vitro .We measured cysteinyl leukotrienes released by phorbol 12-myristate 13-acetate (PMA)–activated human eosinophils or epithelial cells (human bronchial epithelial cell line -BEAS-2B)cultured alone or together.While activated BEAS-2B cells barely formed leukotrienes (1.39 pg/ml ± 0.2))(n=32),activated eosinophils produced considerable amount of them (62.25 pg/ml ± 10.29))(n=32).Interestingly,when activated eosinophils and epithelial cells were co-incubated,production of cysteinyl leukotrienes increased substantially (571.1 pg/ml ± 80.9))(n=32).Thus,eosinophil-epithelial cell interactions,when occur,are associated with increased biosythesis of cysteinyl leukotrienes.
The presented study describes renal tubular epithelial cells morphology in rats during adriamycin therapy. It was demonstrated that one dose of the compound can induce increasing-with time-apoptosis in the cells. A statistically-significant increase in the number of apoptotic cells was observed in experimental groups compared to controls. The highest percentage of apoptotic cells was found in rats 7 weeks after adriamycin administration. The number of apoptotic cells in these animals was statistically significantly higher than that in the rats 4 weeks after adriamycin administration.
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Mammary gland growth and involution is based on a dynamic equilibrium between proliferation and apoptosis of mammary gland epithelial cells (MEC). TGF-ß1 is an important antiproliferative and apoptogenic factor for mammary gland epithelial cells, acting in auto/paracrine matter and thus considered an important local regulator of mammary tissue involution. So far the studies on mammary gland involution concerned only apoptosis as a type I of MEC programmed cell death (PCD). Autophagy is known to be type II of PCD and this paper is the first, supporting evidence for the TGF-ß1-induced autophagy in bovine mammary epithelial cell line BME-UV1, as a distinct to apoptosis type of PCD. Laser scanning cytometry and confocal microscopy were used for analysis of MAP1 LC3 and Beclin1 expression - two proteins considered being the most reliable biochemical markers of autophagy. The significant increase of MAP1 LC3 and Beclin1 expression in cells treated with TGF-ß1 (2 ng/ml) was observed. Ultrastructural observation in electron microscopy revealed that autophagy is not only alternative, but also complementary to apoptosis type of cell death in TGF-ß1-treated bovine MEC. It was manifested by typical morphological features of apoptosis (cell shrinkage, margination and condensation of chromatin) and autophagy (autophagosomes, autophagic vacuoles) in the same cell.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. The initial step in the inflammatory process is overexpression of adhesion molecules, which leads to excessive transmigration of neutrophils. One of these adhesion molecules is ICAM-1 which is elevated in COPD patients. In this study we evaluated the influence of N-acetylcysteine (NAC) (0.01 mM-30 mM) on the cytokine-induced (TNF-alphalpha/IL-1ß) expression of the ICAM-1 adhesion molecule and on IL-8 release in endothelial (ECV-304) and bronchial epithelial (H292) cell lines. The methodology used consisted of immunochemistry for the assessment of surface ICAM-1 and ELISA method for that of soluble ICAM-1 and IL-8. NAC inhibited the TNF-alphalpha/IL-1ß-stimulated ICAM-1 expression and IL-8 release from both cell lines in a concentration dependent manner. The most effective concentrations were 30 mM and 20 mM (99 and 90% inhibition respectively, P<0.01). We conclude that NAC is an effective inhibitor of TNF-alphalpha/IL-1ß- stimulated ICAM-1 and IL-8 release in endothelial and epithelial cells. This fact highlights the anti-inflammatory potential of NAC in COPD.
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