Mitogen-activated protein kinase phosphatase-1 prevents lipopolysaccharide-induced apoptosis in immature rat intestinal epithelial cells

Talavera, María; Kralik, Nathaniel; Jin, Y.; Chen, Bernadette; Liu, Yusen; Nelin, Leif D.

doi:10.1038/pr.2015.88

Cited by 14 publications

(16 citation statements)

References 45 publications

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“…However, the effect of EGF on oxidative stress and apoptosis in porcine IECs under damage condition is still poorly understood. Hence, we used LPS, a major integral component of the outer membrane of Gram-negative bacteria, which can induce cell injury [ 11 , 12 , 13 , 14 ], to establish a cell injury model to investigate the protective effects of EGF on oxidative injury and apoptosis in IPEC-J2 cells. In the present study, we first evaluated the toxicity of EGF and LPS in IPEC-J2 cells; the results showed that EGF at 100 ng/mL can significantly increase cell growth, which is consistent with our previous study, wherein EGF at 100 ng/mL inhibited NaPi-IIb expression [ 27 ], and LPS at 1.0 μg/mL caused a dramatic decrease of cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…Normal cells have a variety of defense mechanisms including, but not limit to, non-enzymatic antioxidant systems (such as ascorbic acid, vitamin E, and glutathione) and enzymatic antioxidant systems (such as superoxide dismutase (SOD), catalase (CAT), and Glutathione peroxidase (GSH-Px)) [ 9 , 10 ]. LPS, a major integral component of the outer membrane of Gram-negative bacteria, has been shown to increase oxidative injury in IECs by producing numerous ROS, which can lead to lipid peroxidation and apoptosis [ 11 , 12 , 13 , 14 ]. The present study used LPS to establish a cell injury model to study the protective effects of EGF on IPEC-J2 cells.…”

Section: Introductionmentioning

confidence: 99%

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Epidermal Growth Factor, through Alleviating Oxidative Stress, Protect IPEC-J2 Cells from Lipopolysaccharides-Induced Apoptosis

Tang

Liu

Wang

et al. 2018

IJMS

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The epidermal growth factor (EGF) has been widely used for protection of stress-induced intestinal mucosa dysfunction. However, whether EGF would alleviate oxidative injury and reduce apoptosis in porcine intestine is not yet known. Therefore, the aim of this study was to investigate the effect of EGF on lipopolysaccharides (LPS)-induced induction of oxidative stress and ensuing apoptosis in the porcine intestinal epithelial cell line, IPEC-J2. The present study showed that EGF significantly increased cell viability and decreased the LPS-induced induction of apoptosis, dehydrogenase (LDH) release and malonaldehyde (MDA) production. EGF also (i) decreased expression of the pro-apoptotic genes Fas, Bax, Cascase-3, Cascase-8, Cascase-9, and proteins such as P53, Fas, Bax, Caspase3; (ii) increased antiapoptotic protein B-cell lymphoma 2 (Bcl2) expression; (iii) increased mRNA levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) related genes Nrf2, manganese superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase (HO-1) and quinone oxidoreductase (NQO1); (iv) protein level of Nrf2-realeted proteins Nrf2, HO-1, NQO1; and (v) total antioxidant capacity (T-AOC), CAT, SOD, GSH-Px concentrations. Collectively, our results indicated that EGF enhanced Nrf2 protein expression, and upregulated the expression of phase II metabolizing enzymes (such as HO-1 and NQO1) and antioxidative enzymes (SOD, CAT and GSH-Px) to alleviate oxidative injury, and then protect IPEC-J2 cells from apoptosis induced by LPS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor, through Alleviating Oxidative Stress, Protect IPEC-J2 Cells from Lipopolysaccharides-Induced Apoptosis

Tang

Liu

Wang

et al. 2018

IJMS

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“…RNA was isolated from rIEC-6 cells, as previously described (Talavera et al, 2015 ). Briefly, 0.7 ml of TRIzol Reagent (Invitrogen, Carlsbad, CA) was added to cells and incubated for 5 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…We used two different models of inflammation in these studies to induce iNOS and arginase. The first was direct treatment with lipopolysaccharide (LPS) to these cells as previously described (Talavera et al, 2015 ) and the second was to incubate the intestinal epithelial cells in conditioned media (CM) obtained from macrophages treated with LPS for 4 h. The LPS treatment gives insight into the direct effect of LPS on intestinal epithelial cells, while the CM, which would contain a mixture of cytokines and chemokines, provides insight into what may occur in the intestinal mileu during inflammation.…”

Section: Introductionmentioning

confidence: 99%

Immunostimulated Arginase II Expression in Intestinal Epithelial Cells Reduces Nitric Oxide Production and Apoptosis

Talavera

Nuthakki

Cui

et al. 2017

Front. Cell Dev. Biol.

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Increased production of nitric oxide (NO) and subsequent local cytotoxicity to mucosal epithelial cells has been proposed as a putative mechanism involved in the development of necrotizing enterocolitis (NEC). Intestinal epithelial cells (IECs) metabolize L-arginine to either nitric oxide (NO) by NO synthase (NOS) or to L-ornithine and urea by arginase. L-ornithine is the first step in polyamine synthesis important for cell proliferation, while NO production can lead to apoptosis. We hypothesized that in IECs immunostimulation increases both NOS and arginase expression, and that arginase activity mitigates NO production and apoptosis. Rat intestinal epithelial cells (rIEC-6) were immunostimulated by either incubation with lipopolysaccharide (LPS) alone for 24 h or by incubation with conditioned media (CM) for 24 h. CM was obtained from RAW 264.7 cells (a macrophage cell line) treated with LPS (E. coli 0127:B8; 1 μg/ml) for 4 h. The rIEC-6 stimulated with LPS or with CM had significantly higher levels of inducible NOS (iNOS) protein, NO production, and arginase II protein than did the control cells. Direct LPS stimulation of rIEC-6 produced a less robust increase in iNOS expression and NO (represented as nitrite percent of control) than did CM stimulation. Inhibition of arginase using Nω hydroxyl-L-arginine (NOHA) further increased stimulated NO production in rIEC-6. Viable cell numbers were significantly lower in CM stimulated cells after 24 h than in controls, and inhibition of arginase activity with NOHA resulted in a further significant decrease in viable cell numbers. We conclude that immunostimulated arginase expression of rIEC-6 cells tempers cytokine-induced iNOS-derived NO production and apoptosis.

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“…The MAPK family can be classified into extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Signaling by these pathways govern fundamental cellular responses, such as cell proliferation, differentiation, inflammation, and apoptosis [11-12]. …”

Section: Introductionmentioning

confidence: 99%

Clostridium Tyrobutyricum Protect Intestinal Barrier Function from LPS-Induced Apoptosis via P38/JNK Signaling Pathway in IPEC-J2 Cells

Zhang¹,

Liu²,

Tao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The intestinal mucosa forms a physical and metabolic barrier against the diffusion of pathogens, toxins, and allergens from the lumen into the circulatory system. Early weaning, a critical phase in swine production, can compromise intestinal barrier function through mucosal damage and alteration of tight junction integrity Maintenance of intestinal barrier function plays a pivotal role in optimum gastrointestinal health. In this study, we investigated the effects of Clostridium tyrobutyricum (C.t) on intestinal barrier dysfunction induced by lipopolysaccharide (LPS) and the underlying mechanisms involved in intestinal barrier protection. Methods: A Transwell model of IPEC-J2 cells was used to imitate the intestinal barrier. Fluorescence microscopy and flow cytometry were used to evaluate apoptosis. Real-time PCR was used to detect apoptosis-related genes and the downstream genes of the p38/c-Jun N-terminal kinase (JNK) signaling pathways. Western blotting was used to measure the expressions of tight junction proteins and mitogen-activated protein kinases. Results: C.t efficiently maintained trans-epithelium electrical resistance values and intestinal permeability after LPS-induced intestinal barrier disruption. The expressions of tight junction proteins (ZO-1, claudin-1, and occludin) were promoted when IPEC-J2 cells were treated with C.t. Fluorescence imaging and flow cytometry revealed that C.t qualitatively and quantitatively inhibited LPS-induced cell apoptosis. C.t also increased the relative expression of the anti-apoptotic gene Bcl-2 and decreased that of the apoptotic genes Bax and caspase-3/-8. Moreover, the protective effect of C.t on damaged intestinal cell models was associated with suppression of p38 and JNK phosphorylation, negative regulation of the relative expressions of downstream genes including AP-1, ATF-2, ELK-1, and p53, and activation of Stat3 expression. Conclusions: These findings indicate that C.t may promote intestinal integrity, suggesting a novel probiotic effect on intestinal barrier function.

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Mitogen-activated protein kinase phosphatase-1 prevents lipopolysaccharide-induced apoptosis in immature rat intestinal epithelial cells

Cited by 14 publications

References 45 publications

Epidermal Growth Factor, through Alleviating Oxidative Stress, Protect IPEC-J2 Cells from Lipopolysaccharides-Induced Apoptosis

Epidermal Growth Factor, through Alleviating Oxidative Stress, Protect IPEC-J2 Cells from Lipopolysaccharides-Induced Apoptosis

Immunostimulated Arginase II Expression in Intestinal Epithelial Cells Reduces Nitric Oxide Production and Apoptosis

Clostridium Tyrobutyricum Protect Intestinal Barrier Function from LPS-Induced Apoptosis via P38/JNK Signaling Pathway in IPEC-J2 Cells

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