Tumour necrosis factor-α-induced loss of intestinal barrier function requires TNFR1 and TNFR2 signalling in a mouse model of total parenteral nutrition

Background & Aims: Our previous studies have provided evidence that p38 mitogen-activated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease. Methods: A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications.Intestinal barrier function was evaluated by transepithelial electrical resistance (TER) and paracellular permeability in Caco-2 cells. The palmitic acid (PA) was used to induce hepatic lipoapoptosis in vitro. The lipoapoptosis was detected using Caspase-3/7 and lipid staining. Results: In the present study, we showed that SB203580 treatment significantly suppressed TPN-mediated intestinal permeability in rats. SB203580 treatment significantly inhibited IL-1β-induced an increase in tight junction permeability of Caco-2 cells via repressing the p38/ATF-2 signaling. Unexpectedly, SB203580 treatment enhanced hepatic lipoapoptosis in the model of TPN. Palmitic acid (PA)-induced hepatic lipoapoptosis in human liver cells was significantly augmented by the SB203580 treatment. Conclusions: We demonstrate that the p38 MAPK inhibitor SB203508 ameliorates intestinal barrier function but promotes hepatic lipoapoptosis in model of TPN.

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Effects of enteral nutrition on pro-inflammatory factors and intestinal barrier function in patients with acute severe pancreatitis

European Journal of Inflammation ◽

10.1177/2058739219827212 ◽

2019 ◽

Vol 17 ◽

pp. 205873921982721 ◽

Cited By ~ 1

Author(s):

Ying-Jie Chen ◽

Yao-Dong Zhuang ◽

Zhe Cai ◽

You-Ni Zhang ◽

Sen-Ren Guo

Keyword(s):

Enteral Nutrition ◽

Parenteral Nutrition ◽

Barrier Function ◽

Tumor Necrosis ◽

Intestinal Barrier ◽

Inflammatory Factors ◽

Intestinal Barrier Function ◽

Acute Severe Pancreatitis ◽

Severe Pancreatitis ◽

Necrosis Factor

The main objective of this study was to explore the effect of enteral nutrition on serum pro-inflammatory cytokines, tumor necrosis factor, and intestinal barrier function in patients with acute severe pancreatitis. A total number of 140 patients were recruited and divided randomly into parenteral nutrition (PN) and enteral nutrition (EN) groups. They received parenteral nutrition and enteral nutrition, respectively. The levels of serum total protein (TP) and albumin (ALB) in peripheral blood were detected in the two groups. Interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) in the two groups were comparatively analyzed. The levels of pro-inflammatory factors (IL-1β, IL-6, and TNFα) for both groups were same, and there was no significant difference ( P < 0.05) between the two groups before treatment. However, after treatment, a significant reduction was found in EN group which were 31.16 ± 1.95, 36.09 ± 9.44, and 29.21 ± 3.85 ng/L, respectively, showing significant lower values as compared to PN group. The levels of TP and ALB in EN group were 64.46 ± 3.77 and 27.19 ± 1.56 g/L, respectively, after treatment, showing significantly ( P < 0.05) elevated values than PN group. The incidence rates of pancreatic necrosis and pancreatic abscess in EN group were 28.57% and 11.43%, respectively, which were found to be lower significantly than PN group. Enteral nutrition is found to be more effective than parenteral nutrition in the treatment of severe acute pancreatitis, which can significantly reduce the level of pro-inflammatory factors as well as the degree of systemic inflammatory response and protect the intestinal barrier function; thus, this study is worthy for awareness and application in clinical practice.

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Tumour necrosis factor receptor-associated factors: interacting protein with forkhead-associated domain inhibition decreases inflammatory cell infiltration and cardiac remodelling after acute myocardial infarction

Interactive CardioVascular and Thoracic Surgery ◽

10.1093/icvts/ivaa060 ◽

2020 ◽

Vol 31 (1) ◽

pp. 85-92 ◽

Cited By ~ 1

Author(s):

Yicheng Jiang ◽

Xue Li ◽

Hai Xu ◽

Yang Gu ◽

Feiya Shi ◽

...

Keyword(s):

Myocardial Infarction ◽

Mouse Model ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Cardiac Remodelling ◽

Tumour Necrosis Factor Receptor ◽

Tumour Necrosis Factor Α ◽

Interacting Protein ◽

Factor Α ◽

Necrosis Factor

Abstract OBJECTIVES Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Post-AMI cardiac remodelling is closely related to the prognosis of AMI. The excess inflammatory responses could promote cardiac remodelling. Tumour necrosis factor receptor-associated factor-interacting protein with forkhead-associated domain (TIFA) has been identified as a nuclear factor (NF)-κB activator, which plays a key role in the activation of the NF-κB signalling pathway. The goal of this research was to investigate the expression and the underlying mechanism of TIFA in an AMI mouse model. METHODS The AMI mouse model was induced by ligation of the left coronary artery. TIFA and NF-κB knockdown were established by lentivirus transduction. The expression levels of associated proteins were analysed by a western blot or an enzyme-linked immunosorbent assay. Histological characteristics were evaluated by haematoxylin–eosin staining. RESULTS The TIFA level was elevated in our AMI mouse model. The production of interleukin-1β and tumour necrosis factor-α increased markedly in the mice with AMI. TIFA knockdown inhibited the infiltration of inflammatory cells, production of pro-inflammatory mediators (interleukin-1β and tumour necrosis factor-α), NF-κB activation and cardiac remodelling (matrix metallopeptidase 9) post-AMI. In addition, NF-κB knockdown could also alleviate cardiac remodelling after AMI. CONCLUSIONS The preceding results indicated that TIFA inhibition could ameliorate cardiac remodelling after AMI partly through inactivation of NF-κB. This study provides insights into further research of cardiac remodelling and AMI from bench to clinic.

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Decline in intestinal mucosal IL-10 expression and decreased intestinal barrier function in a mouse model of total parenteral nutrition

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00386.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. G139-G147 ◽

Cited By ~ 76

Author(s):

Xiaoyi Sun ◽

Hua Yang ◽

Keisuke Nose ◽

Satoko Nose ◽

Emir Q. Haxhija ◽

...

Keyword(s):

Parenteral Nutrition ◽

Tight Junction ◽

Total Parenteral Nutrition ◽

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Junction Molecules

Loss of intestinal epithelial barrier function (EBF) is a major problem associated with total parenteral nutrition (TPN) administration. We have previously identified intestinal intraepithelial lymphocyte (IEL)-derived interferon-γ (IFN-γ) as a contributing factor to this barrier loss. The objective was to determine whether other IEL-derived cytokines may also contribute to intestinal epithelial barrier breakdown. C57BL6J male mice received TPN or enteral nutrition (control) for 7 days. IEL-derived interleukin-10 (IL-10) was then measured. A significant decline in IEL-derived IL-10 expression was seen with TPN administration, a cytokine that has been shown in vitro to maintain tight junction integrity. We hypothesized that this change in IEL-derived IL-10 expression could contribute to TPN-associated barrier loss. An additional group of mice was given exogenous recombinant IL-10. Ussing chamber experiments showed that EBF markedly declined in the TPN group. TPN resulted in a significant decrease of IEL-derived IL-10 expression. The expression of several tight junction molecules also decreased with TPN administration. Exogenous IL-10 administration in TPN mice significantly attenuated the TPN-associated decline in zonula occludens (ZO)-1, E-cadherin, and occludin expression, as well as a loss of intestinal barrier function. TPN administration led to a marked decline in IEL-derived IL-10 expression. This decline was coincident with a loss of intestinal EBF. As the decline was partially attenuated with the administration of exogenous IL-10, our findings suggest that loss of IL-10 may be a contributing mechanism to TPN-associated epithelial barrier loss.

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Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

Biochemical Society Symposium ◽

10.1042/bss0700039 ◽

2003 ◽

Vol 70 ◽

pp. 39-52 ◽

Cited By ~ 54

Author(s):

Roy A. Black ◽

John R. Doedens ◽

Rajeev Mahimkar ◽

Richard Johnson ◽

Lin Guo ◽

...

Keyword(s):

Substrate Specificity ◽

Recent Work ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Transforming Growth Factor ◽

Intrinsic Activity ◽

Converting Enzyme ◽

Tumour Necrosis Factor Α ◽

Factor Α ◽

Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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