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The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway

Cellular & Molecular Immunology 2017年第1期14卷 127-142页

作者： Rojo A Ratsimandresy Mohanalaxmi Indramohan Andrea Dorfleutner christian stehlik Division of Rheumatology Department of Medicine Feinberg School of Medicine Northwestern University Chicago IL 60611 USA Robert H. Lurie Comprehensive Cancer Center Interdepartmental Immunobiology Center and Skin Disease Research Center Feinberg School of Medicine Northwestern University Chicago IL 60611 USA

Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.

关键词： antimicrobial peptides IL-18 IL-22 IL-22BP inflammasome inflammatory bowel disease microbiome Reg3

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Proposed EU legislation to force changes in sewage sludge disposal:A case study

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Frontiers of Chemical Science and Engineering 2018年第4期12卷 660-669页

作者： Vojtech Turek Bohuslav Kilkovsky Zdenek Jegla Petr stehlik Institute of Process Engineering Faculty of Mechanical EngineeringBmo University of Tectmology61669 BmoCzech Republic

The consequences of changes planned in the European Union legislation relevant to the disposal of sewage sludges are discussed. A specific municipal waste water treatment plant is analyzed in terms of drying and subsequent combustion or pyrolysis of the produced stabilized sludge, and the respective net energy balances are carried out. A simplified economic analysis of the two disposal options is presented, which suggest that combustion of the sludge would be economically infeasible while pyrolysis of the sludge in a modular, self-sufficient container unit can bring a small financial benefit due to the selling of the produced phosphorus-rich biochar.

关键词： sewage sludge drying combustion pyrolysis

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