scholarly journals The Anti-inflammatory Immune Regulation Induced by Butyrate Is Impaired in Inflamed Intestinal Mucosa from Patients with Ulcerative Colitis

Inflammation ◽  
2019 ◽  
Vol 43 (2) ◽  
pp. 507-517 ◽  
Author(s):  
Maria K. Magnusson ◽  
Stefan Isaksson ◽  
Lena Öhman

Abstract Altered gut microbiota composition and reduced levels of short-chain fatty acids, such as butyrate, have been identified as key components of ulcerative colitis (UC). We aimed to determine and compare effects of butyrate on the intestinal immune profile of UC patients with active disease and non-inflamed controls. Biopsies were cultivated during 6 h with or without butyrate. Cytokines were measured in supernatants and mRNA gene expression was analyzed in biopsies using Qiagen RT2 Profiler PCR Arrays. The intestinal immune profile of cultured biopsies, as determined by mRNA gene expression and secreted cytokines, differed between inflamed UC samples and controls. Principal component analysis revealed that addition of butyrate differently regulated mRNA expression in inflamed biopsies from UC and non-inflamed biopsies from controls. Highly discriminant and predictive orthogonal partial least squares discriminant analyses identified 29 genes for UC (R2 = 0.94, Q2 = 0.86) and 23 genes for controls (R2 = 0.90, Q2 = 0.71) that were most regulated by butyrate. UC displayed more up-regulation of genes as compared with controls, and controls displayed the most prominent down-regulations. Ingenuity Pathway Analysis identified a down regulation of the Neuroinflammation Signaling pathway and predicted inhibition of the categories Inflammatory response, cellular movement, and cellular development as top diseases and functions, respectively, for controls but not for UC. In conclusion, butyrate has a different effect on gene regulation and more potently down-regulates gene expression of inflammatory pathways in non-inflamed controls than in inflamed tissue of UC patients. These discrepancies may at least partly explain why anticipated anti-inflammatory effects of local butyrate induction or supplementation are not always obtained.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Anja Sandek ◽  
Joe Wüst ◽  
Juergen Bauditz ◽  
Stephan von Haehling ◽  
Alexander Swidsinski ◽  
...  

Background: Chronic heart failure (CHF) is a state of chronic inflammation. High serum levels of TNF alpha and the presence of cardiac cachexia are known to predict poor survival in CHF. Abnormal balance of pro- and anti-inflammatory circulating cytokine mRNA gene expression is thought to contribute to cachexia in humans, but has never been studied in CHF patients. Methods and Results: We studied 7 patients with cardiac cachexia (age 70±4 years, LVEF 28±2%, peak VO2 12.7±1.6 mL/kg/min, all >6% weight loss in previous 6–24 months), 19 noncachectic CHF patients (age 68±2 years, LVEF 31±2%, peak VO2 14.7±1.1 mL/kg/min) and 17 control subjects of similar age and gender (peak VO2 25.1±1.7 mL/kg/min, LVEF 71±2%). The mRNA gene expression of circulating mononuclear blood cells for pro-inflammatory mediators that have been implicated in the wasting process of ageing (TNF, STAT-1, STAT-3, SOCS-1 and SOCS-3) as well as anti-inflammatory cytokines (IL-10, tumor growth factor (TGF) beta were investigated by real time polymerase chain reaction. Values for the house keeping gene and genes of interest were calculated from double determinations within 40 cycles. We found higher TNF expression in cachectic compared to noncachectic CHF patients (log mean −0.5±0.17 vs. −1.2±0.12, p=0.002, ANOVA-p=0.0071) and control subjects (log mean −1.2±0.1, p=0.006). In contrast, there was no change in IL-10 gene expression in cachectic patients compared to noncachectic patients and controls (log mean −2.6±0.2 vs. −3.0±0.09 vs. −2.9±0.1, all p>0.13). Consequently TNF/IL-10 expression ratio was highest in cachectic patients (308±138 vs. 132±55 in noncachectic CHF patients vs. 101±37 in controls, p<0.004). There were no differences in gene expression of STAT-1, STAT-3, SOCS-1, SOCS-3 between cachectic and noncachectic individuals (all p>0.17). Similarly, no differences were found for gene expression of TGF beta (p>0.15). Conclusion: The balance between the pro-inflammatory cytokine TNF and the anti-inflammatory cytokine IL-10 on the level of mRNA expression of circulating mononuclear cells is significantly disturbed. Proinflammatory cytokine imbalance in cardiac cachexia may be important for the pathophysiology of body wasting and may represent the activated immune reflex.


2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.


2006 ◽  
Vol 82 (6) ◽  
pp. 877-887 ◽  
Author(s):  
J. Sehm ◽  
H. Lindermayer ◽  
H. H. D. Meyer ◽  
M. W. Pfaffl

Flavan-3-ols are a class of flavonoids that are widely distributed in fruits and beverages including red wine and apples. Consumption of flavanoid-rich food has been shown to exhibit anti-microbial, anti-oxidative, anti-inflammatory, and immune-modulating effects. To test the nutritional effects of flavanols on mRNA gene-expression of inflammatory and apoptotic marker genes, piglets were given two flavanoids-rich feeding regimens: a low flavanoid standard diet (SD) was compared with diets enriched with 3·5% apple pomace (APD) or 3·5% red-wine pomace (RWPD). The influence on mRNA expression levels was investigated in different immunological active tissues and in the gastro-intestinal tract (GIT). The investigation took place from 1 week prior weaning to 19 days post weaning in 78 piglets. The expression of expressed marker genes was determinate by one-step quantitative real-time (qRT-PCR): TNFα, NFκB as pro-inflammatory; IL10, as anti-inflammatory; caspase 3 as apoptosis; cyclin D1 as cell cycle marker; and nucleosome component histon H3 as reference gene.The feeding regimens result in tissue individual regulation of mRNA gene expression in all investigated organs. It was discovered that there were significant differences between the applied diets and significant changes during feeding time curse. Both pomace treatments caused a significant up-regulation of all investigated genes in liver. The effect on mesenterial lymph nodes and spleen was not prominent. In the GIT, the treatment groups showed a inhibitory effects on gene expression mainly in stomach and jejunum (NFκB, cyclin D1 and caspase 3). In colon the trend of caspase 3 was positive with the greatest change in the RWPD group.In jejunum and stomach the cell cycle turn over was reduced, whereas in liver the cell turn over was highly accelerate. The influence on inflammatory marker gene expression is mainly relevant in stomach. It is presume that both flavanoid rich feeding regimens have the potential to modulate the mRNA expressions of inflammatory, proliferation and apoptotic marker genes in the GIT and piglet organs.


2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Sarah Wilson ◽  
Tianli Zhu ◽  
Rajesh Khanna ◽  
Michael Pritz

AbstractGene expression was investigated in the major brain subdivisions (telencephalon, diencephalon, midbrain and hindbrain) in a representative reptile, Alligator mississipiensis, during the later stages of embryonic development. The following genes were examined: voltage-gated sodium channel isoforms: NaV1.1 and NaV1.2; synaptic vesicle 2a (SV2a); synaptophysin; and calbindin 2. With the exception of synaptophysin, which was only expressed in the telencephalon, all genes were expressed in all brain regions sampled at the time periods examined. For NaV1.1, gene expression varied according to brain area sampled. When compared with NaV1.1, the pattern of NaV1.2 gene expression differed appreciably. The gene expression of SV2a was the most robust of any of the genes examined. Of the other genes examined, although differences were noted, no statistically significant changes were found either between brain part or time interval. Although limited, the present analysis is the first quantitative mRNA gene expression study in any reptile during development. Together with future experiments of a similar nature, the present gene expression results should determine which genes are expressed in major brain areas at which times during development in Alligator. When compared with other amniotes, these results will prove useful for determining how gene expression during development influences adult brain structure.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3909
Author(s):  
Melissa S. Totten ◽  
Derek M. Pierce ◽  
Keith M. Erikson

The aim of this study was to determine the impact of diet-induced obesity (DIO) on trace element homeostasis and gene expression in the olfactory bulb and to identify potential interaction effects between diet, sex, and strain. Our study is based on evidence that obesity and olfactory bulb impairments are linked to neurodegenerative processes. Briefly, C57BL/6J (B6J) and DBA/2J (D2J) male and female mice were fed either a low-fat diet or a high-fat diet for 16 weeks. Brain tissue was then evaluated for iron, manganese, copper, and zinc concentrations and mRNA gene expression. There was a statistically significant diet-by-sex interaction for iron and a three-way interaction between diet, sex, and strain for zinc in the olfactory bulb. Obese male B6J mice had a striking 75% increase in iron and a 50% increase in manganese compared with the control. There was an increase in zinc due to DIO in B6J males and D2J females, but a decrease in zinc in B6J females and D2J males. Obese male D2J mice had significantly upregulated mRNA gene expression for divalent metal transporter 1, alpha-synuclein, amyloid precursor protein, dopamine receptor D2, and tyrosine hydroxylase. B6J females with DIO had significantly upregulated brain-derived neurotrophic factor expression. Our results demonstrate that DIO has the potential to disrupt trace element homeostasis and mRNA gene expression in the olfactory bulb, with effects that depend on sex and genetics. We found that DIO led to alterations in iron and manganese predominantly in male B6J mice, and gene expression dysregulation mainly in male D2J mice. These results have important implications for health outcomes related to obesity with possible connections to neurodegenerative disease.


2002 ◽  
Vol 30 (5) ◽  
pp. A123-A123
Author(s):  
C.L. Curtis ◽  
S.G. Rees ◽  
C. Wilson ◽  
R. Williams ◽  
C. Dent ◽  
...  

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