Project description:Nf-kB activity is associated with the key pathological features of chronic respiratory diseases including epithelial remodelling, excess mucous production, and submucosal gland hyperplasia. However, the role of Nf-kB activity in airway epithelial differentiation remains controversial. In the present study we demonstrate that Nf-kB adaptor protein Myd88 deficiency promotes increased airway submucosal gland abundance and abnormal epithelial differentiation in proximal adult airways. Abnormal airway differentiation was not developmentally determined, became exacerbated following acute lung injury, and did not involve altered epithelial proliferation or apoptosis. Instead, we demonstrate that tracheal Myd88 deficiency promotes upregulation of a unique gene expression profile that includes activation of alternate, Myd88-independent Nf-kB signalling. Finally, we show that these effects are not intrinsically maintained in vitro using an air-liquid interface epithelial culture. This finding indicates that Myd88 deficiency promotes adult airway remodelling by regulating non-epithelial, non-cell autonomous Nf-kB activity. 20 microarray samples of whole trachea RNA in total: 5 samples wildtype control tissue 5 samples Myd88 KO control tissue 5 samples wildtype 3 day polidocanol injury tissue 5 samples Myd88 KO 3 day polidocanol injury tissue
Project description:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
Project description:Comparison of gene expression in wildtype and MyD88-/- C57BL/6J mouse macrophages treated with 10 ng/mL LPS for 2 hours versus media treated control macrophages, and, wildtype and MyD88-/- C57BL/6J mouse macrophages treated with live E. coli bacteria (log phase; 1 bact per 1 macrophage) for 2 hours versus media treated control macrophages. Cells from 4 mice of each geneotype were used and each individual provided its own control. Hybridizations of treated and control samples from each mouse were dye swap replicated. Wildtype macrophages treated with LPS vs control (GSM22617-GSM22623,GSM22625), MyD88-/- macrophages treated with LPS vs control (GSM22626-GSM22632), wldtype macrophages treated with E. coli vs control (GSM22633-GSM22640, and MyD88-/- macrophages treated with E. coli vs control (GSM22641-GSM22648). Keywords: other
