Interleukin-1ß (IL-1ß) promotes susceptibility of Toll-like receptor 5 (TLR5) deficient mice to colitis.

BACKGROUND: The extent to which numerous strains of genetically engineered mice, including mice lacking Toll-like receptor 5 (T5KO), display colitis is environment dependent. Gut microbiota underlie much of the variation in phenotype. Accordingly, embryonic rederivation of T5KO mice ameliorated their spontaneous colitis despite only partially correcting elevated proinflammatory gene expression. It was postulated that endogenous anti-inflammatory pathways mediated the absence of overt inflammation in these mice when their gut microbiota were reset. Consequently, it was hypothesised that neutralisation of the anti-inflammatory cytokine interleukin 10 (IL-10) might induce uniform colitis in T5KO mice, and thus provide a practical means to study mechanisms underlying their inflammation. METHODS: Two distinct strains of non-colitic T5KO mice, as well as mice lacking MyD88, Toll-like receptor 4 (TLR4), IL-1 receptor (IL-1R) and various double knockouts (DKOs) were treated weekly for 4 weeks with 1 mg/mouse of IL-10 receptor neutralising antibody (IL-10R mAb) and colitis assayed 1 week later. The composition of the caecal microbiota was determined by 454 pyrosequencing of 16S rRNA genes. RESULTS: Anti-IL-10R mAb treatment led to severe uniform intestinal inflammation in both strains of T5KO mice. Such neutralisation of IL-10 signalling did not cause colitis in wild-type littermates nor mice lacking TLR4, MyD88 or IL-1R. The susceptibility of T5KO mice to this colitis model was not rescued by absence of TLR4 in that T4/T5 DKO mice displayed severe colitis in response to anti-IL-10R mAb treatment. IL-1ß signalling was crucial for this colitis model in that IL-1R/T5 DKOs were completely protected from colitis in response to IL-10R mAb treatment. Lastly, it was observed that blockade of IL-10R function was associated with changes in the composition of gut microbiota, which were observed in mice that were susceptible and resistant to IL-10R mAb-induced colitis. CONCLUSION: Regardless of whether they harbour a colitogenic microbiota, loss of TLR5 predisposes mice to colitis triggered by immune dysregulation via an IL-1ß-dependent pathway.

Very-High Color Rendering Index Hybrid White Organic Light-Emitting Diodes with Double Emitting Nanolayers.

A very-high color rendering index white organic light-emitting diode (WOLED) based on a simple structure was successfully fabricated. The optimized device exhibits a maximum total efficiency of 13.1 and 5.4 lm/W at 1,000 cd/m2. A peak color rendering index of 90 and a relatively stable color during a wide range of luminance were obtained. In addition, it was demonstrated that the 4,4',4″-tri(9-carbazoyl) triphenylamine host influenced strongly the performance of this WOLED. These results may be beneficial to the design of both material and device architecture for high-performance WOLED.

Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice.

Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis.

Isolation and identification of pelteobagrin, a novel antimicrobial peptide from the skin mucus of yellow catfish (Pelteobagrus fulvidraco).

Fish skin mucus has recently been recognized to be a potential source of antimicrobial peptides, which provides the first line of defense against invading pathogens. This study reports the purification and characterization of a novel linear antimicrobial peptide, pelteobagrin, from the skin mucus of yellow catfish (Pelteobagrus fulvidraco, Richardson). Pelteobagrin is 20 amino acids in length (GKLNLFLSRLEILKLFVGAL) and shows no clear homology with any known bioactive peptides. MALDI-TOF MS indicated the molecular mass of the purified peptide was 2244.4 Da, which is in good agreement with pelteobagrin's predicted molecular weight of 2244.8 Da. Pelteobagrin exhibited antibacterial activity against Gram-positive and Gram-negative bacteria as well as fungi, and the activity was relatively salt-insensitive as it was not affected by NaCl concentrations of up to 137 mM. Moreover, pelteobagrin displayed no hemolytic activity to rabbit red blood cells. Transmission electron microscopy suggested that pelteobagrin might kill bacteria via acting on both the cell wall and the cytoplasmic membrane of bacteria. These results suggest that pelteobagrin might be involved in the innate defense system in yellow catfish.