scholarly journals The Dynamic Changes of Gut Microbiota in Muc2 Deficient Mice

2018 ◽  
Vol 19 (9) ◽  
pp. 2809 ◽  
Author(s):  
Minna Wu ◽  
Yaqi Wu ◽  
Jianmin Li ◽  
Yonghua Bao ◽  
Yongchen Guo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
High Throughput Sequencing ◽  
Interleukin 1 ◽  
Colorectal Carcinogenesis ◽  
Dynamic Changes ◽  
Intestinal Pathology ◽  
Factor Α ◽  
I Kappa B Kinase

Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis, and the genetic deficiency of the Muc2 gene causes spontaneous development of colitis and colorectal cancer. Whether there are changes of gut microbiota and a linkage between the changes of microbiota and intestinal pathology in Muc2−/− mice are unclear. Muc2−/− and Muc2+/+ mice were generated by backcrossing from Muc2+/− mice, and the fecal samples were collected at different dates (48th, 98th, 118th, 138th, and 178th day). Gut microbiota were analyzed by high-throughput sequencing with the universal 16S rRNA primers (V3–V5 region). All mice were sacrificed at day 178 to collect colonic tissue and epithelial cells for the analysis of histopathology and inflammatory cytokines. On the 178th day, Muc2−/− mice developed colorectal chronic colitis, hyperplasia, adenomas and adenocarcinomas, and inflammatory cytokines (e.g., cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 1 β (IL-1β), i-kappa-B-kinase β (IKKβ)) were significantly increased in colonic epithelial cells of Muc2−/− mice. In general, structural segregation of gut microbiota was observed throughout the experimental time points between the Muc2−/− and Muc2+/+ mice. Impressively, in Muc2−/− mice, Alpha diversities reflected by Shannon and Chao indexes were higher, the phylum of Firmicutes was enriched and Bacteroidetes was decreased, and Desulfovibrio, Escherichia, Akkermansia, Turicibacter, and Erysipelotrichaceae were significantly increased, but Lactobacilli and Lachnospiraceae were significantly decreased. Moreover, the abundance of Ruminococcaceae and butyrate-producing bacteria was significantly higher in the Muc2−/− mice. There were significant differences of gut microbiota between Muc2−/− and Muc2+/+ mice. The dynamic changes of microbiota might contribute to the development of colitis and colitis-associated colorectal carcinogenesis. Therefore, this study revealed specific functional bacteria in the development of colitis and colitis-associated colorectal carcinogenesis, which will benefit the development of preventive and therapeutic strategies for chronic inflammation and its malignant transformation.

WY-14 643, a Selective PPARα Agonist, Induces Proinflammatory and Proangiogenic Responses in Human Ocular Cells

2010 ◽  
Vol 29 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Jin-Zhong Zhang ◽  
Keith W. Ward
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Peroxisome Proliferator ◽  
Cytokine Release ◽  
Corneal Epithelial Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Corneal Epithelial ◽  
Factor Α ◽  
Endothelial Growth Factor ◽  
Pparα Agonist

Peroxisome proliferator-activated receptor α (PPARα) agonism in ocular inflammation has not been thoroughly investigated. The objective of this investigation was to determine the effect of WY-14 643, a selective PPARα agonist, on inflammatory cytokine release in human ocular cells. Stimulation of primary human corneal epithelial cells, keratocytes, and retinal endothelial cells with 1 to 10 ng/mL interleukin 1β (IL-1β) resulted in a significant increase in numerous inflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor α (TNF-α); and dexamethasone was able to significantly inhibit these effects. However, WY-14 643 did not effectively block IL-1β-induced cytokine release in ocular cells; rather, significant increases in IL-1β-induced inflammatory cytokines were observed in these cells but not in aortic smooth muscle cells. WY-14 643 also significantly upregulated vascular endothelial growth factor (VEGF) expression in corneal epithelial cells and keratocytes. These studies demonstrate for the first time that PPARα agonism may be proinflammatory and proangiogenic in a variety of ocular cells and suggest that therapeutic applications of such agents in ophthalmology may be limited.

scholarly journals Chlorogenic Acid and Geniposide Combination Prevents NASH in Rats Fed High-fat diet via Microbiota and TLR4-LPS Pathway

2021 ◽  
Author(s):  
Zhijia Zhou ◽  
Lingxia Xu ◽  
Shaoliang Zhang ◽  
Shilin Xu ◽  
Yanmiao Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Chlorogenic Acid ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Oral Treatment ◽  
Variable Region ◽  
High Fat ◽  
Tnf Α ◽  
Abundance And Diversity ◽  
Factor Α

Abstract Objective: Chlorogenic acid and geniposide (CG) are derived from traditional Chinese medicine, Yinchenhao Recipe (QCHR), and can improve the clinical efficacy of NASH patients. This study investigated the effects of CG on NASH and expounded its Potential mechanism of action through the LPS-TLR4 pathway and microbiota. Methods: Rats were randomized into Control (C), Model (M), Chlorogenic Acid and Geniposide (CG), Pioglitazone (PH) and Bifico (B) groups. After an 8-week high-fat diet (HFD), CG, PH and B oral treatment were initiated and carried out for a further 8 weeks. The stool samples were used in a16S rDNA V4 highly variable region measurement method in order to regulate the role of CG in gut microbiota. The concentrations of triglyceride (TG), cholesterol (CHO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in LPS were detected by the corresponding methods. Results: Observations were made that CG significantly improved the pathology of the liver and terminal ileum tissue. The accumulation of TG and the content of inflammatory cytokines in the liver were significantly decreased and the abundance of Proteobacteria was significantly down-regulated. The expression of TLR4, AP-1, MyD88, and phosphorylated NF-κB p65 were significantly decreased. All the findings above indicated that CG was highly effective in improving the composition of gut microbiota, decreasing the production of endogenous LPS, and reducing the secretion of inflammatory cytokines through the gut-liver axis.Conclusion: CG can regulate the abundance and diversity of the intestinal microbial community and improve liver inflammation and steatosis in NASH rats by reducing LPS-TLR4-mediated inflammation.

scholarly journals Corrigendum: The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2 (Diabetes mellitus. 2019;22(3). doi: 10.14341/DM10194)

2019 ◽  
Vol 22 (4) ◽  
pp. 403-404
Author(s):  
Elena V. Pokrovskaya ◽  
Minara S. Shamkhalova ◽  
Marina V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Diabetes Mellitus Type 2 ◽  
Interleukin 1 ◽  
The State ◽  
Diabetes Mellitus Type ◽  
Obesity And Diabetes ◽  
Anti Inflammatory

A corrigendum on The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2 by Elena V. Pokrovskaya, Minara S. Shamkhalova, Marina V. Shestakova (2019). Diabetes Mellitus. 22(3). doi: 10.14341/DM10194There is an error on the page 255: "Moreover, in obese patients, the concentration of circulating LPS increases by 20%, and in patients with diabetes mellitus, it increases by 125%. LPS is transported from cells of the large intestine into the bloodstream through chylomicrons or through intercellular gaps in the intestinal wall; by forming a complex of CD14 with Toll-like receptor 4 of macrophages and endothelial cells, it causes the release of anti-inflammatory cytokines: namely, interleukin-1, interleukin-6 and tumour necrosis factor alpha ". Instead of " pro-inflammatory cytokines" was published " anti-inflammatory cytokines ".Literary source Dahiya DK, Renuka, Puniya M, et al. Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review. Front Microbiol. 2017;8:563. doi: https://doi.org/10.3389/fmicb.2017.00563 is listed twice (№№ 7 and 13) in the list of references.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.

scholarly journals Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

2017 ◽  
Vol 42 (3) ◽  
pp. 1109-1119 ◽  
Author(s):  
Xudong Sun ◽  
Xue Yuan ◽  
Liang Chen ◽  
Tingting Wang ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Transcriptional Activity ◽  
Interleukin 1 ◽  
Common Disease ◽  
Pyrrolidine Dithiocarbamate ◽  
Bovine Rumen ◽  
Rumen Epithelial Cells ◽  
Cells Cultured

Background/Aims: Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.

scholarly journals Secretion of Ferritin by Rat Hepatoma Cells and Its Regulation by Inflammatory Cytokines and Iron

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4979-4986 ◽  
Author(s):  
Tue N. Tran ◽  
Sharon K. Eubanks ◽  
Kenneth J. Schaffer ◽  
Cecilia Y.J. Zhou ◽  
Maria C. Linder
Keyword(s):  
Inflammatory Cytokines ◽  
Serum Ferritin ◽  
Interleukin 1 ◽  
Brefeldin A ◽  
Acute Phase Reactant ◽  
Hepatoma Cells ◽  
Hepatic Cells ◽  
Factor Α ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells

Abstract The possibility that serum ferritin is a secreted protein and an acute phase reactant regulated by inflammatory hormones and iron was examined in a hepatic cell line that secretes plasma proteins. Differentiated rat hepatoma cells released albumin and ferritin into the medium, as determined by rocket immunoelectrophoresis and isolation of ferritin by standard procedures plus immunoaffinity chromatography, following labeling with radioactive amino acid. Administration of interleukin-1–β (IL-1) or tumor necrosis factor-α (TNF) doubled the amounts of ferritin released into the medium over 24 and 48 hours. Together, the cytokines had more than an additive effect. Albumin secretion was diminished by IL-1, but not TNF. Iron, administered as an iron dextran complex or as a 1:1 chelate with nitrilotriacetate (Fe-NTA), also enhanced ferritin release, but had no effect on albumin. Intracellular ferritin concentrations did not change significantly with cytokine treatment, but increased in response to iron. With or without treatments, release of ferritin and albumin from cells into the medium was inhibited by brefeldin A, an inhibitor of Golgi function. The effect of each of the cytokines and of iron on ferritin and albumin was also blocked by dichlorofuranosylbenzimidazole (DRB), an inhibitor of transcription. The stimulatory effect of Fe-NTA on ferritin secretion was diminished by TNF, and this was partially counteracted by IL-1, indicating additional regulatory complexity. These results show for the first time that hepatic cells secrete ferritin, that this ferritin secretion is regulated by iron and inflammatory cytokines, and that the mechanisms of regulation differ from those for intracellular ferritin. The results would explain why serum ferritin increases in inflammation or when iron flux is enhanced.

scholarly journals Secretion of Ferritin by Rat Hepatoma Cells and Its Regulation by Inflammatory Cytokines and Iron

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4979-4986 ◽  
Author(s):  
Tue N. Tran ◽  
Sharon K. Eubanks ◽  
Kenneth J. Schaffer ◽  
Cecilia Y.J. Zhou ◽  
Maria C. Linder
Keyword(s):  
Inflammatory Cytokines ◽  
Serum Ferritin ◽  
Interleukin 1 ◽  
Brefeldin A ◽  
Acute Phase Reactant ◽  
Hepatoma Cells ◽  
Hepatic Cells ◽  
Factor Α ◽  
Rat Hepatoma ◽  
Rat Hepatoma Cells

The possibility that serum ferritin is a secreted protein and an acute phase reactant regulated by inflammatory hormones and iron was examined in a hepatic cell line that secretes plasma proteins. Differentiated rat hepatoma cells released albumin and ferritin into the medium, as determined by rocket immunoelectrophoresis and isolation of ferritin by standard procedures plus immunoaffinity chromatography, following labeling with radioactive amino acid. Administration of interleukin-1–β (IL-1) or tumor necrosis factor-α (TNF) doubled the amounts of ferritin released into the medium over 24 and 48 hours. Together, the cytokines had more than an additive effect. Albumin secretion was diminished by IL-1, but not TNF. Iron, administered as an iron dextran complex or as a 1:1 chelate with nitrilotriacetate (Fe-NTA), also enhanced ferritin release, but had no effect on albumin. Intracellular ferritin concentrations did not change significantly with cytokine treatment, but increased in response to iron. With or without treatments, release of ferritin and albumin from cells into the medium was inhibited by brefeldin A, an inhibitor of Golgi function. The effect of each of the cytokines and of iron on ferritin and albumin was also blocked by dichlorofuranosylbenzimidazole (DRB), an inhibitor of transcription. The stimulatory effect of Fe-NTA on ferritin secretion was diminished by TNF, and this was partially counteracted by IL-1, indicating additional regulatory complexity. These results show for the first time that hepatic cells secrete ferritin, that this ferritin secretion is regulated by iron and inflammatory cytokines, and that the mechanisms of regulation differ from those for intracellular ferritin. The results would explain why serum ferritin increases in inflammation or when iron flux is enhanced.

Bifico Relieves Irritable Bowel Syndrome By Regulating Gut Microbiota Dysbiosis and Inflammatory Cytokines in an Animal Model

2021 ◽  
Author(s):  
Yanlin Zhou ◽  
Fan Zhang ◽  
Liqi Mao ◽  
Tongfei Feng ◽  
Kaijie Wang ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Short Chain Fatty Acids ◽  
Intragastric Administration ◽  
Protein Levels ◽  
Tnf Α ◽  
Irritable Bowel ◽  
Factor Α ◽  
Gut Microbiota Dysbiosis

Abstract Gut microbiota dysbiosis, a core pathophysiology of irritable bowel syndrome (IBS), is closely related to immunological and metabolic functions. Gut microbiota-based therapeutics have been recently explored in several studies. Bifico is a probiotic cocktail widely used in gastrointestinal disorders which relate to the imbalance of gut microbiota. However, the efficacy and potential mechanisms of Bifico treatment in IBS remains incompletely understood. In this animal experiment, IBS mice received Bifico by intragastric administration. Subsequently, abdominal withdrawal reflex (AWR) scores showed a protective effect of Bifico in IBS mice. Then 16S rDNA, 1H nuclear magnetic resonance (1H-NMR) and western blot assays were performed to analyze alterations of gut microbiota, microbiome metabolites and inflammatory cytokines, respectively. Results suggested that while Bifico did not increase gut microbial diversity, it could change the composition of gut microbiota which were characterized by an increase of Proteobacteria phylum and Actinobacteria phylum, Muribaculum genera, Bifidobacterium genera and a decrease of Parabacteroides genera, Sutterella genera and Lactobacillus genera. Moreover, Bifico elevated the concentration of short-chain fatty acids (SCFAs) and reduced protein levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). From further Spearman's correlation analysis, Bifidobacterium genera were positively correlated with SCFAs including propionate, butyrate, valerate and negatively correlated with IL-6 and TNF-α. In conclusion, this study demonstrated that Bifico could alleviate symptoms of IBS mice through regulation of the gut microbiota, elevating production of SCFAs and reducing the colonic inflammatory response. Therefore, Bifico may have utility in clinical practice.

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