Silencing of peroxiredoxin 1 expression ameliorates ulcerative colitis in a rat model

Background Peroxiredoxin 1 (PRDX1), a protein with anti-inflammatory and anti-apoptotic properties, shows elevated expression in ulcerative colitis (UC). However, PRDX1's specific role in UC is poorly understood. Methods UC was induced in rats using dextran sulfate sodium (DSS). In vivo RNA interference was used to silence the PRDX1 expression. PRDX1 expression levels and the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and interferon (IFN)-γ in tissues were assessed by real-time quantitative polymerase chain reaction and western blotting. Colonic injury was assessed by hematoxylin–eosin staining. ELISA was used to assess levels of the inflammatory cytokines TNF-α, IL-1β and IL-6 in colon tissues. Apoptosis of intestinal epithelial cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling, and expression of the apoptotic proteins bcl-2, Bax, cleaved caspase-3 and caspase-3 was assessed by western blotting. Results PRDX1 expression was significantly increased in rats with DSS-induced UC. Silencing of PRDX1 expression improved colon injury in rats with DSS-induced UC. In addition, silencing of PRDX1 expression inhibited inflammatory responses and apoptosis of intestinal epithelial cells in rats with DSS-induced UC. Conclusions Silencing of PRDX1 expression can ameliorate colon injury in rats with DSS-induced UC.

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Effect of Berberine from Coptis chinensis on Apoptosis of Intestinal Epithelial Cells in a Mouse Model of Ulcerative Colitis: Role of Endoplasmic Reticulum Stress

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3784671 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Shen Yan ◽

Liu Yingchao ◽

Wang Zhangliu ◽

Ruan Xianli ◽

Li Si ◽

...

Keyword(s):

Ulcerative Colitis ◽

Endoplasmic Reticulum ◽

Epithelial Cells ◽

Endoplasmic Reticulum Stress ◽

Caspase 3 ◽

Intestinal Epithelial Cells ◽

High Dose ◽

Intestinal Epithelial ◽

Model Group ◽

Caspase 12

The purpose of this study was to verify the effect of berberine (BBR) on endoplasmic reticulum stress (ERS) and apoptosis of intestinal epithelial cells (IECs) in mice with ulcerative colitis (UC). BALB/c mice were randomly divided into five groups as follows: blank control, model, and low-, medium-, and high-dose BBR. A dextran sodium sulfate- (DSS-) induced model of UC was prepared, and the low-, medium-, and high-dose BBR groups were simultaneously gavaged with a BBR suspension for 7 d. Disease activity index (DAI) was assessed, and tissue damage index (TDI) was assessed from colon samples after the last administration. TUNEL assays were used to detect apoptosis of IECs. Immunohistochemistry and/or real-time PCR were applied to determine the expression of GRP78, caspase-12, and caspase-3. In all BBR treatment groups, clinical symptoms of colitis and histopathological damage were significantly reduced. The high-dose BBR group exhibited particularly pronounced decrease (p<0.01) in both DAI (0.48 ± 0.36) and TDI (1.62 ± 0.64) relative to the model group (1.50 ± 0.65 and 3.88 ± 0.04, respectively). In colon tissues of the model group, the number of apoptotic IECs was significantly increased; the expression of GRP78, caspase-12, and caspase-3 proteins was significantly increased; and the expression of the GRP78 mRNA was upregulated. In low-, medium-, and high-dose BBR groups, the number of apoptotic IECs was significantly reduced. Moreover, GRP78 and caspase-3 expression levels were significantly decreased in the medium- and high-dose BBR groups, caspase-12 expression was significantly decreased in the high-dose BBR group, and the GRP78 mRNA expression level was significantly decreased in the high-dose BBR group. BBR can effectively reduce the rate of IEC apoptosis in UC mice and alleviate the inflammatory response in the colon. The underlying mechanism seems to involve ERS modulation and inhibition of ERS-mediated activation of the caspase-12/caspase-3 apoptosis signaling pathway.

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miR-200b-3p alleviates TNF-α-induced apoptosis and inflammation of intestinal epithelial cells and ulcerative colitis progression in rats via negatively regulating KHDRBS1

Cytotechnology ◽

10.1007/s10616-021-00490-3 ◽

2021 ◽

Vol 73 (5) ◽

pp. 727-743

Author(s):

Chunju Zheng ◽

Ting Lu ◽

Zhimin Fan

Keyword(s):

Ulcerative Colitis ◽

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Tnf Α ◽

Induced Apoptosis ◽

Apoptosis And Inflammation

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NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion

AJP Cell Physiology ◽

10.1152/ajpcell.00480.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. C1009-C1018 ◽

Cited By ~ 67

Author(s):

Tongtong Zou ◽

Jaladanki N. Rao ◽

Xin Guo ◽

Lan Liu ◽

Huifang M. Zhang ◽

...

Keyword(s):

Epithelial Cells ◽

Caspase 3 ◽

Intestinal Epithelial Cells ◽

Specific Inhibitor ◽

Inhibitory Effect ◽

Intestinal Epithelial ◽

Tnf Α ◽

Induced Apoptosis ◽

Necrosis Factor ◽

Active Caspase

Apoptosis plays a crucial role in maintenance of intestinal epithelial integrity and is highly regulated by numerous factors, including cellular polyamines. We recently showed that polyamines regulate nuclear factor (NF)-κB activity in normal intestinal epithelial (IEC-6) cells and that polyamine depletion activates NF-κB and promotes resistance to apoptosis. The current study went further to determine whether the inhibitors of apoptosis (IAP) family of proteins, c-IAP2 and XIAP, are downstream targets of activated NF-κB and play a role in antiapoptotic activity of polyamine depletion in IEC-6 cells. Depletion of cellular polyamines by α-difluoromethylornithine not only activated NF-κB activity but also increased expression of c-IAP2 and XIAP. Specific inhibition of NF-κB by the recombinant adenoviral vector containing IκBα superrepressor (Ad Iκ BSR) prevented the induction of c-IAP2 and XIAP in polyamine-deficient cells. Decreased levels of c-IAP2 and XIAP proteins by inactivation of NF-κB through Ad Iκ BSR infection or treatment with the specific inhibitor Smac also overcame the resistance of polyamine-depleted cells to apoptosis induced by the combination of tumor necrosis factor (TNF)-α and cycloheximide (CHX). Although polyamine depletion did not alter levels of procaspase-3 protein, it inhibited formation of the active caspase-3. Decreased levels of c-IAP2 and XIAP by Smac prevented the inhibitory effect of polyamine depletion on the cleavage of procaspase-3 to the active caspase-3. These results indicate that polyamine depletion increases expression of c-IAP2 and XIAP by activating NF-κB in intestinal epithelial cells. Increased c-IAP2 and XIAP after polyamine depletion induce the resistance to TNF-α/CHX-induced apoptosis, at least partially, through inhibition of the caspase-3 activity.

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TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

BMC Gastroenterology ◽

10.1186/1471-230x-9-53 ◽

2009 ◽

Vol 9 (1) ◽

Cited By ~ 56

Author(s):

Irina Treede ◽

Annika Braun ◽

Petia Jeliaskova ◽

Thomas Giese ◽

Joachim Füllekrug ◽

...

Keyword(s):

Epithelial Cells ◽

Inflammatory Cytokines ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Tnf Α ◽

Pro Inflammatory Cytokines

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Protective effects of baicalin on LPS-induced injury in intestinal epithelial cells and intercellular tight junctions

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0262 ◽

2015 ◽

Vol 93 (4) ◽

pp. 233-237 ◽

Cited By ~ 24

Author(s):

Jian Chen ◽

Ren Zhang ◽

Jian Wang ◽

Peng Yu ◽

Quan Liu ◽

...

Keyword(s):

Epithelial Cells ◽

Protein Expression ◽

Tight Junctions ◽

Inflammatory Cytokines ◽

Intestinal Epithelial Cells ◽

Expression Level ◽

Protective Effects ◽

Intestinal Epithelial ◽

Tnf Α ◽

Mrna And Protein Expression

Aims: To investigate the protective effects and mechanisms of baicalin on lipopolysaccharide (LPS)-induced injury in intestinal epithelial cells and intercellular tight junctions. Methods: IEC-6 cells were stimulated with LPS (1.0 μg/mL), with or without baicalin, for 24 h. The levels of the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were determined using ELISA. Quantitative real-time PCR was used for determining the mRNA expression level of claudin-3, occludin, and ZO-1; Western blot and immunofluorescence analysis were used for analyzing the expression level and the distribution patterns of ZO-1 protein. Results: Pretreatment with baicalin (10.0 μg/mL) improved LPS-stimulated cell viability and repressed IL-6 and TNF-α levels. In addition, pretreatment with baicalin up-regulated mRNA and protein expression levels of ZO-1 and kept the protein intact in IEC-6 cells injured with LPS. Conclusion: Baicalin has the capacity to protect IEC-6 cells and the intercellular tight junctions from LPS-induced injury. The mechanisms may be associated with inhibiting the production of inflammatory cytokines, and up-regulating the mRNA and protein expression of ZO-1.

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