19 research outputs found
Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation. miR-223-/y mice presented with exacerbated myeloid-driven experimental colitis with heightened clinical, histopathological, and cytokine readouts. Mechanistically, enhanced NLRP3 inflammasome expression with elevated IL-1β was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2+ inflammatory monocytes and pharmacologic blockade of IL-1β or NLRP3 abrogated this phenotype. Generation of a novel mouse line, with deletion of the miR-223 binding site in the NLRP3 3′ untranslated region, phenocopied the characteristics of miR-223-/y mice. Finally, nanoparticle-mediated overexpression of miR-223 attenuated experimental colitis, NLRP3 levels, and IL-1β release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation
TGF-β1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis
Barrier dysfunction has been implicated in the pathophysiology of eosinophilic esophagitis (EoE). TGF-β1, a potent pleiotropic molecule, is increased in EoE, however, no study has evaluated its influence on esophageal epithelial barrier. We hypothesized that TGF-β1 regulates barrier dysfunction in EoE. We aimed to determine the role of TGF-β1 in epithelial barrier in models of EoE. To examine the impact of TGF-β1 on esophageal barrier, immortalized human esophageal epithelial (EPC2-hTERT) cells were exposed to TGF-β1 during the 3-dimensional air liquid interface (3D-ALI) model in vitro. TGF-β1 exposure diminished EPC2-hTERT barrier function as measured by transepithelial electrical resistance (TEER) and 3kDa FITC dextran paracellular flux (FITC Flux) and H&E assessment revealed prominent cellular separation. In analysis of epithelial barrier molecules, TGF-β1 led to the specific reduction in expression of the tight-junction molecule, claudin-7 and this was prevented by TGF-β receptor I inhibitor. shRNA mediated claudin-7 knockdown diminished epithelial barrier function, while claudin-7 overexpression resulted in protection from TGF-β1-mediated barrier dysfunction. In analysis of pediatric EoE biopsies claudin-7 expression was decreased, altered localization was observed by immunofluorescence analysis and the TGF-β1 downstream transcription factor phosphorylated SMAD2/3 (pSMAD2/3) was increased. Our data suggest that TGF-β1 participates in esophageal epithelial barrier dysfunction through claudin-7 dysregulation
Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis
Epithelial barrier dysfunction is a significant factor in many allergic diseases, including eosinophilic esophagitis (EoE).
Infiltrating leukocytes and tissue adaptations increase metabolic demands and decrease oxygen availability at barrier
surfaces. Understanding of how these processes impact barrier is limited, particularly in allergy. Here, we identified a
regulatory axis whereby the oxygen-sensing transcription factor HIF-1α orchestrated epithelial barrier integrity, selectively
controlling tight junction CLDN1 (claudin-1). Prolonged experimental hypoxia or HIF1A knockdown suppressed HIF-1α–
dependent claudin-1 expression and epithelial barrier function, as documented in 3D organotypic epithelial cultures. L2-IL5OXA
mice with EoE-relevant allergic inflammation displayed localized eosinophil oxygen metabolism, tissue hypoxia, and impaired
claudin-1 barrier via repression of HIF-1α/claudin-1 signaling, which was restored by transgenic expression of esophageal
epithelial-targeted stabilized HIF-1α. EoE patient biopsy analysis identified a repressed HIF-1α/claudin-1 axis, which was
restored via pharmacologic HIF-1α stabilization ex vivo. Collectively, these studies reveal HIF-1α’s critical role in maintaining
barrier and highlight the HIF-1α/claudin-1 axis as a potential therapeutic target for EoE
Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis
Epithelial barrier dysfunction is a significant factor in many allergic diseases, including eosinophilic esophagitis (EoE).
Infiltrating leukocytes and tissue adaptations increase metabolic demands and decrease oxygen availability at barrier
surfaces. Understanding of how these processes impact barrier is limited, particularly in allergy. Here, we identified a
regulatory axis whereby the oxygen-sensing transcription factor HIF-1α orchestrated epithelial barrier integrity, selectively
controlling tight junction CLDN1 (claudin-1). Prolonged experimental hypoxia or HIF1A knockdown suppressed HIF-1α–
dependent claudin-1 expression and epithelial barrier function, as documented in 3D organotypic epithelial cultures. L2-IL5OXA
mice with EoE-relevant allergic inflammation displayed localized eosinophil oxygen metabolism, tissue hypoxia, and impaired
claudin-1 barrier via repression of HIF-1α/claudin-1 signaling, which was restored by transgenic expression of esophageal
epithelial-targeted stabilized HIF-1α. EoE patient biopsy analysis identified a repressed HIF-1α/claudin-1 axis, which was
restored via pharmacologic HIF-1α stabilization ex vivo. Collectively, these studies reveal HIF-1α’s critical role in maintaining
barrier and highlight the HIF-1α/claudin-1 axis as a potential therapeutic target for EoE
Comparison of kinetics of acetone, heptane and toluene photocatalytic mineralization over TiO2 microfibers and Quartzel® mats
International audienceThe kinetic parameters for VOCs (acetone, toluene, heptane) mineralization of lab-extruded pure TiO2fibers prepared under easily scalable conditions were compared with those of a commercial photo-catalytic media from Saint-Gobain, Quartzel®, under identical conditions. A flow-through recirculatingreactor loop with variable LEDs irradiation at 365 nm was specially designed. All the experiments werecarried out in a continuous recycle mode. Both types of fibers were very efficient for acetone and hep-tane mineralization. At 20% relative humidity (RH), the reaction rates were higher with the commercialmedia, whereas at 60% RH the catalysts displayed equal activity for acetone conversion. Toluene min-eralization was much faster on these lab-made fibers than on Quarztel®, which was more sensitiveto poisoning by reaction by-products. At 20% relative humidity, with the lab-made TiO2fibers, typicalquantum efficiencies were, respectively, 0.0106 and 0.0027 for acetone and heptane (100 ppmV initialconcentration) and 0.0024 for toluene (200 ppmV initial concentration) while these quantum efficiencieswere 0.0358, 0.0133 and 0.0011 with expanded Quartzel fibers under the same conditions. These resultsevidence a clear difference in the VOCs, water and polar by-products adsorption between these two kindsof fibers.These newly developed fibers can be produced at an industrial scale with a proven efficiency for VOCsdegradation and mineralization. Since they are less sensitive to humidity than the commercial fibers,they could be most useful under actual ambient air conditions. These fibers present a good alternative toother commercially available photocatalytic media for gas phase purification
Orientation controllable growth of MoO3 nanoflakes: Micro-raman, field emission, and birefringence properties
10.1021/jp907602wJournal of Physical Chemistry C1134720259-2026
EVOLUTION OF TEMPORAL ISOLATION IN THE WILD: GENETIC DIVERGENCE IN TIMING OF MIGRATION AND BREEDING BY INTRODUCED CHINOOK SALMON POPULATIONS
Eosinophils and IL-33 Perpetuate Chronic Inflammation and Fibrosis in a Pediatric Population with Stricturing Crohn’s Ileitis
Background: Fibrostenosis and stricture are well-recognized endpoints in Crohn’s disease (CD). We hypothesized that stricturing CD is characterized
by eosinophilia and epithelial IL-33. We proposed that eosinophil exposure to IL-33 would perpetuate inflammatory chronicity and subsequent
fibrostenosis.
Methods: We performed a retrospective study of 74 children with inflammatory and stricturing ileal CD comparing clinicopathological features to
immunohistochemical measures of eosinophilia and IL-33. To scrutinize eosinophil patterns, we developed a novel eosinophil peroxidase score
encompassing number, distribution, and degranulation. Human eosinophils and intestinal fibroblasts were cultured with IL-33 and IL-13, and inflammatory
and remodeling parameters were assessed. Antieosinophil therapy was also administered to the Crohn’s-like ileitis model (SAMP1/SkuSlc).
Results: Our novel eosinophil peroxidase score was more sensitive than H&E staining, revealing significant differences in eosinophil patterns, comparing
inflammatory and stricturing pediatric CD. A significant relationship between ileal eosinophilia and complicated clinical/histopathological phenotype
including fibrosis was determined. IL-33 induced significant eosinophil peroxidase secretion and IL-13 production. Exposure to eosinophils in the presence
of IL-33, “primed” fibroblasts to increase proinflammatory cytokines (TNF-a, IL-1b, and IL-6), eosinophil-associated chemokines (CCL24 and CCL26), and
IL-13Ra2 production. Production of fibrogenic molecules (collagen 1A2, fibronectin, and periostin) increased after exposure of “primed” fibroblasts to
IL-13. Epithelial-IL-33 was increased in pediatric Crohn’s ileitis and strongly associated with clinical and histopathological activity, ileal eosinophilia, and
complicated fibrostenotic disease. SAMP1/SkuSlc eosinophil-targeted treatment resulted in significant improvements in inflammation and remodeling.
Conclusions: Our study of specimens from pediatric patients with ileal CD linked eosinophil patterns and IL-33 to fibrosis and suggested that these
may contribute to the perpetuation of inflammation and subsequent stricture in pediatric CD
Varying TiO2 Macroscopic Fiber Morphologies toward Tuning Their Photocatalytic Properties
In a context of volatile organic compound photodecomposition, we haveaddressed TiO2-based macroscoscpic fiber generation. We have extruded hybrid sols ofamorphous titania nanoparticles, latex nanoparticles, and nonionic surfactant (Tergitol) as structure-directing agents into a poly(vinyl alcohol) (PVA) solution bearing salts acting as a flocculating medium. The resulting nanocomposite TiO2/latex/PVA macroscopic fibers were thermally treated in air to open porosity by organic removal while generating the photocatalytically active anatase phase of TiO2 along with residual brookite. Considering the synthetic paths, we have varied both the diameter of the latex particles as well as their concentration within the starting sol. These parameters allow tuning both the voids created through the applied thermal treatment and the fiber final diameters. For gas-phase photocatalysis, we have shown that the fiber diameters, mesoscopic roughness, and macroscopic topological defects represent indeed important orphological parameters acting cooperatively toward both acetone degradation and its mineralization processes. Particularly, triggering the fiber morphological characteristics, we have increased their efficiency toward acetone degradation of around 550% when compared with previous work