200 resultados para Fetal fibroblasts
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Given the spread of antibiotic resistance in bacterial pathogens, antimicrobial peptides that can also modulate the immune response may be a novel approach for effectively controlling periodontal infections. In the present study, we used a three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) to investigate the anti-inflammatory properties of human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) and to determine whether these antimicrobial peptides can act in synergy. The 3D co-culture model composed of gingival fibroblasts embedded in a collagen matrix overlaid with gingival epithelial cells had a synergistic effect with respect to the secretion of IL-6 and IL-8 in response to LPS stimulation compared to fibroblasts and epithelial cells alone. The 3D co-culture model was stimulated with non-cytotoxic concentrations of hBD-3 (10 and 20 mu M) and LL-37 (0.1 and 0.2 mu M) individually and in combination in the presence of A. actinomycetemcomitans LPS. A multiplex ELISA assay was used to quantify the secretion of 41 different cytokines. hBD-3 and LL-37 acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IP-10, IL-6, and MCP-1, but only had an additive effect on reducing the secretion of IL-8 in response to A. actinomycetemcomitans LPS stimulation. The present study showed that hBD-3 acted in synergy with LL-37 to reduce the secretion of cytokines by an LPS-stimulated 3D model of gingival mucosa. This combination of antimicrobial peptides thus shows promising potential as an adjunctive therapy for treating inflammatory periodontitis.
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Maternal undernutrition affects the foetal development, promoting renal alterations and adult hypertension. The present study investigates, in adult male rats, the effect of food restriction in utero on arterial blood pressure changes (AP), and its possible association with the number of nephrons, renal function and angiotensin II (AT1R/AT2R), glucocorticoid (GR) and mineralocorticoid (MCR) receptors expression. The daily food supply to pregnant rats was measured and one group (n=5) received normal quantity of food (NF) while the other group received 50% of that (FR50) (n=5). The AP was measured weekly. At 16 weeks of life, fractionator’s method was used to estimate glomeruli number in histological slices. The renal function was estimate by creatinine and lithium clearances. Blood and urine samples were collected to biochemical determination of creatinine, sodium, potassium and lithium. At 90th and 23rd days of life, kidneys were also processed to AT1R, AT2R, GR and MCR immunolocalization and for western blotting analysis. FR50 offspring shows a significant reduction in BW (FR50: 5.67 ± 0.16 vs. 6.84 ± 0.13g in NF, P<0.001) and increased AP from 6th to 12nd week (6thwk FR50: 149.1 ± 3.4 vs. 125.1 ± 3.2mmHg in NF, P<0.001and, 12ndwk FR50: 164.4 ± 4.9 vs. 144.0 ± 3.3 mmHg in NF, P=0.02). Expression of AT1R and AT2R were significantly decreased in FR50 (AT1, 59080 ± 2709 vs. 77000 ± 3591 in NF, P=0.05; AT2, 27500 ± 95.50 vs. 67870 ± 1509 in NF, P=0.001) while the expression of GR increased in FR50 (36090 ± 781.5 vs. 4446 ± 364.5 in NF, P=0.0007). The expression of MCR did not change significantly. We also verified a pronounced decrease in fractional urinary sodium excretion in FR50 offspring (0.03 ± 0.02 vs. 0.06 ± 0.04 in NF, p=0.03). This occurred despite unchanged creatinine clearance. The study led us to suggest that fetal undernutrition, with increased fetal exposure... (Complete abstract click electronic access below)