IMMUNOMODULATION AND INTESTINAL BARRIER PROTECTION ACTIVITIES OF A NOVEL SYNTHETIC GLUCOSE ANALOGUE IN INFLAMMATORY ANIMAL MODEL OF COLITIS AND ASTHMA [article]

GIUSEPPINA DUSIO
2010
1. INTRODUCTION 1.1. In vivo 2.2.1. Mice 2.2.2. Experimental model of sepsis 2.2.3. Induction of acute and chronic colitis 2.2.4. Enzyme-linked immunosorbent assay 2.2.5. Immunofluorescence analysis in tissue 2.3. Statistical analysis 3. MATERIALS AND METHODS BLF501 role in lung inflammation 3.1. Cell lines and treatments 3.1.1. Coculture of HT-29 and human MoDCs 3.1.2. Small interfering RNA (siRNA) 3.2. Mice and in vivo treatments 3.2.1. Exposure of mice to aerosolized LPS 3.2.2. Asthma model
more » ... .2.2. Asthma model 3.2.3. Bronchoalveolar lavage (BALF) 3.2.4. Hematoxylin-eosin staining 3.2.5. Immunohistochemistry 3.2.6. Immunofluorescence assay 3.2.7. Isolation of murine dendritic cells 3.3. Enzyme-linked immunosorbent assays (ELISA) 3.3.1. hsp/hsp25 ELISA 3.4. Western blot analysis 3.5. Statistical analysis 4 4. RESULTS 4.1. Synthetic glucose analogues: synthesis and screening 4.1.1. Stability studies 4.1.2. BLF501 affects LPS-induced IL-8 release in intestinal epithelial cells 4.1.3. Protection afforded by BLF501 in LPS-induced shock in mice 4.2. SGLT-1 a new therapeutic target for epithelial barrier function 4.2.1. SGLT-1 activation by BLF-501 5 µg/l effects on permeability of Caco-2 monolayer against inflammatory stimuli (INF-γ and TNF-α) and "chemical-DSS" damage 4.2.2. BLF501-mediated barrier functionality protection is associated to a morphological conservation of two TJ proteins 4.2.3. BLF501 protection against inflammatory bowel disease in vivo 4.3. SGLT-1 a new therapeutic target in lung inflammatory disease 4.3.1. Engagement of SGLT-1 inhibits the response of human pneumocytes to LPS BLF501 inhibits LPS-induced interleukin IL-8 production in human pneumocytes A549 cells at 100,000-fold lower concentrations than D-glucose Protective anti-inflammatory effects induced by BLF501 engagement of SGLT-1 in lung after aerosol administration of LPS Anti-inflammatory effects of BLF501 in an OVA-induced model of allergic asthma 4.3.5. Orally administered BLF501 inhibits OVA-induced lung inflammation 4.3.6. Hsp27 mediates the anti-inflammatory effects of BLF501 through induction of IL-10 production by dendritic cells 5 5. DISCUSSION 5.1. Dansyl C-Glycoside as a novel agent against endotoxic shock 5.2. BLF501 as a novel agent against colitis animal model 5.3. BLF501 as a novel agent against inflammatory lung disease 6. REFERENCES Fig 17 (A) Rapresentative colonic H&E section from mice receiving water without DSS . a) Lamina mucosa; b)Lamina submucosa; c)Circular and longitudinal mussle. In magnification arrow shows colon crypte with normal morphology and black arrowhead indicates globet cells. (B) Colon histology from DSS-treated group. DSS induces thickening of the colon wall, globet cells and crypt loss in large areas (in magnification arrow). Infiltration reaching the lamina submucosa (withe arrow). (C) Representative colon section of glucose 2,5 g/kg treatment in acute colitis. Normal morphology with low level of inflammation (D) H&E of BLF501 250 µg/kg and (E) BLF501 25 µg/kg, histologically comparable with control group. Bar 50 µm
doi:10.13130/dusio-giuseppina_phd2010-12-20 fatcat:ifmlcbxtn5aynnmljyp6lqm5wa