Andrew Neish

..We hypothesize that many of the known effects of the normal microbiota on intestinal physiology, and potential beneficial effects of candidate probiotic bacteria, may be at least partially mediated by this ROS-dependent mechanism...

....

....

..These data suggest that prokaryotic determinants could be responsible for the unique tolerance of the gastrointestinal mucosa to proinflammatory stimuli...

....

..Also important are potential mechanisms by which microbes can influence the intestinal epithelial responses, influences with significant implications for the normal function of the intestine and inflammatory diseases...

..Recent delineation of the mechanisms by which bacteria communicate with their eukaryotic hosts and the cellular sites that microbial signals act in may shed light on these complex interactions...

....

..This notion is consistent with the emerging paradigm that specific TLR ligands may have a fundamental cytoprotective effect during inflammatory stress...

..All together, these results indicate that the resistance of TLR5KO mice to Salmonella-induced typhoid-like illness resulted from alterations in their basal phenotype rather than from the lack of TLR5 ligation during the infection per se...

....

..Thus, systemic administration of flagellin may be a relatively safe means of providing temporary non-specific protection against a variety of challenges...

..Such intertwining of proinflammatory and apoptotic signaling mediated by bacterial products suggests roles for host programmed cell death in the pathogenesis of enteric infections...

..Our findings suggest that targeting JNK signaling to dampen apoptosis may be a conserved strategy for intracellular pathogens...

..That an engineered innate immune deficiency ultimately results in spontaneous intestinal inflammation supports the notion that an innate immune deficiency might underlie some instances of inflammatory bowel disease...

..Because apoptosis may be a precursor to NEC, understanding the mechanism behind probiotic modulation of apoptotic pathways may allow for development of more specifically targeted therapies or preventive strategies in the future...

....

..Thus, S. typhimurium flagellin is the major molecular trigger by which this pathogen activates gut epithelial proinflammatory gene expression...

....

..Thus, the characteristic inflammatory pathology of Salmonella infection occurs only in PPs and to a lesser extent in MLN during the initial phases of infection and these early responses are dependent on TLR5...

..This work demonstrates that a useful panel of immunohistochemical markers can be derived from differential gene expression profiles determined using cDNA microarrays...

..Thus, LXA(4) analog-mediated down-regulation of proinflammatory gene expression via inhibition of the NF-kappaB pathway can be therapeutic for diseases characterized by mucosal inflammation...

..Thus, TLR5's rapid activation of PI3K serves to limit MAPK signaling, thus limiting proinflammatory gene expression and reducing the potential negative consequences of proinflammatory gene expression...

....

....

....

..Together, these results indicate that epithelial cell induction of flagellin-specific gene expression is mediated, in part, by STAT activation that results from autocrine activation via IL-6...

....

..Together, these results indicate that epithelial TLR5 mediates p38 activation and subsequently regulates flagellin-induced IL-8 expression independently of NF-kappaB, probably by influencing IL-8 mRNA translation...

..This observation may explain the ability of intestinal bacterial communities to influence diverse eukaryotic processes in general and inflammatory tolerance of the mammalian intestinal epithelia specifically...

..These findings could form the basis for the development of electroporation as a clinical tool to increase intestinal permeability and, thereby, increase the absorption of poorly absorbed drugs...

..These data suggest that nonvirulent bacterial-epithelial interactions can influence beta-catenin signaling and cell growth control in a manner previously unsuspected...

..Previously, it has been shown that flagellin limits ionising radiation-induced mortality in mice, but the cellular mechanism of protection remained unknown...

....

..These findings suggest that electroporation may be useful for intracellular delivery into monolayers to study epithelial biology and, possibly, for drug delivery to intestinal epithelium...

..These results show that selective cryptdins may amplify their roles in innate immunity by acting as novel paracrine agonists to coordinate an inflammatory response with the antimicrobial secretions of Paneth cells...

..These results define a molecular regulatory pathway by which Ado provides potent antiinflammatory properties...

..Elucidation of these host-microbe interactions will increase our understanding of the epithelial and bacterial factors involved in human enterocolitis, and potentially in idiopathic inflammatory intestinal disease. ..

..These studies will increase our understanding of the pathogenesis of enteric bacterial infections, and possibly illuminate means by which commensal bacteria contribute to the health of the Gl tract. ..

..Elucidation of these host-microbe interactions will increase our understanding of the epithelial and bacterial factors involved in human enterocolitis, and potentially in idiopathic inflammatory intestinal disease. ..

..These studies will increase our understanding of the pathogenesis of enteric bacterial infections, and possibly illuminate means by which commensal bacteria contribute to the health of the Gl tract. ..

..More significantly, these data will be invaluable in the recognition of these signatures in human diseases potentially associated with infection by known and unknown organisms. ..

..Finally, a novel electroporation based method to introduce purified proteins into intact model epithelia will be used to dissect the cellular responses to internalization of a variety of bacterial effector proteins. ..