Pancreatitis-Associated Ascitic Fluid Induces Proinflammatory Cytokine Expression in THP-1 Cells by Inhibiting Anti-inflammatory Signaling

Wang, Jing; Xu, Ping; Hou, Yan-qiang; Xu, Kai; Li, Qinghua; Huang, Ling

doi:10.1097/mpa.0b013e318279fe5c

Cited by 15 publications

(10 citation statements)

References 27 publications

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“…As is known, PAAF plays an important role during the progression of SAP. It contains a mass of toxic substances including tumor necrosis factor a, interleukin and endotoxin, which can induce pancreatic tissue necrosis and aggravate the inflammatory response [2][3][4][5]. Therefore, various treatment strategies that remove PAAF may be effective in treating SAP [25].…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatic associated ascites fluid (PAAF) is known to play a critical role in the pathogenesis of SAP because it contains various Chen Luo and Qilin Huang have contributed equally to this study. toxic substances such as tumor necrosis factor, interleukin, endotoxin and so on [2][3][4][5]. Our previous clinical and experimental studies showed that abdominal paracentesis drainage (APD) attenuated the outcomes of SAP safely and effectively through removing PAAF [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodiumtaurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP. Keywords APD • Severe acute pancreatitis • Apoptosis • PI3K/AKT signaling pathway Abbreviations AKT(PKB) Protein kinase B ANOVA One-way analysis of variance APD Abdominal paracentesis drainage Bcl-2 B-cell lymphoma 2 Caspase3 Cysteine aspartic acid protease 3 ELISA Enzyme-linked immunosorbent assay IL Interleukin MAP Mild acute pancreatitis MODS Multiple organ dysfunction syndrome NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells PAAF Pancreatitis associated ascitic fluids PI3K Phosphatidylinositide 3-kinases SAP Severe acute pancreatitis SIRS Systemic inflammatory response syndrome TNF-α TNF-α

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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“…It has been reported that the activation of PPAR␥ in immune cells may inhibit NF-B activation and further lead to the downregulation of proinflammatory cytokine expression. Using pancreatitis-associated ascitic fluid to treat THP-1 cells, a human monocytic cell line, the levels of NF-B-p65 and proinflammatory cytokines (i.e., TNF-␣ and IL-6) were increased, whereas the downregulation of PPAR␥ was observed (Wang et al 2013a). Pretreatment with pioglitazone, a ligand of PPAR␥, could protect rats from acute pancreatitis through the downregulation of NF-Binduced proinflammatory cytokines (TNF-␣ and IL-6) .…”

Section: Fig 2 Effects Of a Membranaceus On The Antibody Levels Ofmentioning

confidence: 96%

Astragalusmembranaceusmodulates Th1/2 immune balance and activates PPARγ in a murine asthma model

Chen

Tsai

Lee

et al. 2014

Biochem. Cell Biol.

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Astragalus membranaceus, a traditional Chinese herb, has been used to improve airway inflammation and asthma. The present study investigated whether A. membranaceus has immunotherapeutic effects on asthma, a chronic inflammatory mucosal disease that is associated with excess production of IgE, eosinophilia, T helper 2 (Th2) cytokines, and bronchial hyperresponsiveness. An ovalbumin (OVA)-induced, chronic inflammatory airway murine asthma model was used to examine the status of pulmonary inflammation after the administration of A. membranaceus. The IgE levels in serum and bronchoalveolar lavage fluid showed a tendency to decrease after the administration of A. membranaceus. The number of eosinophils decreased and infiltration of inflammatory cells and collagen deposition declined in lung sections after A. membranaceus administration. The RNA and protein levels of Th2 cytokines and the ratio of the GATA3/T-bet mRNA levels decreased after A. membranaceus treatment. Furthermore, the mRNA level of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, increased in the lung tissues of A. membranaceus-treated mice. Finally, an A. membranaceus water extract activated PPARγ activity in either human embryonic kidney 293 (HEK293) or A549 cells in a PPARγ-responsive element-containing luciferase reporter assay. These results indicate that A. membranaceus has an inhibitory effect on airway inflammation in a murine model of asthma through modulating the imbalanced relationship between Th1 and Th2 cytokines.

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“…NF-κB and p38MAPK are the two main signaling pathways activated by TLR4-mediated signaling, and both play an important role in the regulation of several inflammatory cytokines and mediators. Previous work from our group has shown that the activation of NF-κB and p38MAPK is a prominent response during pancreatic injury and that activation of these molecules plays a key role not only in the release of inflammatory factors, but also in increasing neutrophil infiltration of the pancreas (14,26). All the above research thus suggests that TLR4 plays an important role in the synthesis and release of proinflammatory cytokines, and indicates that upregulation of the TLR4 gene may be related to the development of inflammation in SAP.…”

Section: Discussionmentioning

confidence: 96%

“…It is well known that NF-κB and p38MAPK play critical roles in regulating the expression of proinflammatory genes such as TNF-α, IL-β and IL-6 (11,12). Our previous findings indicated that these two signaling pathways were activated in SAP rats (2,13) and pancreatitis-associated ascitic fluid stimulated THP-1 cells (14), which was suppressed by wortmannin (2). In the present study, we examined the expression of TLR4, PI3K, Akt, p38MAPK, NF-κBp65 and MyD88 in vivo in SAP rats and in vitro in RAW264.7 murine macrophages (stimulated by LPS) following treatment with the PI3K agonist insulin-like growth factor (IGF)-1, and further explored the possible mechanisms by evaluating the correlation between PI3K/Akt and TLR4 in inflammatory reactions associated with SAP.…”

Section: Introductionmentioning

confidence: 93%

Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis

Wang

Zhang

et al. 2018

Mol Med Report

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Phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) has been indicated to serve an important role in the pathogenesis of inflammatory diseases. It was previously demonstrated that the PI3K/Akt inhibitor wortmannin alleviated the severity of inflammation and improved the survival rate in rats with induced severe acute pancreatitis (SAP), which indicates that PI3K/Akt may serve a role in the pathogenesis of acute pancreatitis. To date, the mechanism by which PI3K/Akt regulates inflammation has not been elucidated. In the present study, it was hypothesized that PI3K/Akt may be invovled in SAP inflammation via regulation of the Toll‑like receptor 4 (TLR4) signaling pathway. Rats with SAP were treated with the PI3K/Akt agonist insulin‑like growth factor (IGF)‑1, which alleviated the severity of inflammation in a dose‑dependent manner. Furthermore, to better understand the role of PI3K/Akt in inflammation, RAW264.7 murine macrophages were stimulated with IGF‑1 and wortmannin alone or together before the induction of inflammation by treatment with lipopolysaccharide (LPS). The results indicated that LPS stimulated overexpression of TLR4, myeloid differentiation primary response gene 88 (MyD88), PI3K, Akt, p38MAPK and NF‑κBp65 mRNA, and increased the levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 in RAW264.7 cells compared with the control group. The levels of all detected factors were increased by stimulation with IGF‑1, whereas these levels were decreased following treatment with wortmannin alone, and the effect of IGF‑1 was abolished by wortmannin in RAW264.7 cells. In vivo studies indicated that IGF‑1 produced the same anti‑inflammatory effect as wortmannin and that expression of TLR4, p38MAPK and NF‑κBp65 decreased following treatment with IGF‑1. These findings indicate that PI3K/Akt may take part in the progression of SAP by regulating the TLR4 signaling pathway and that IGF‑1 can inhibit inflammation in SAP rats.

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Pancreatitis-Associated Ascitic Fluid Induces Proinflammatory Cytokine Expression in THP-1 Cells by Inhibiting Anti-inflammatory Signaling

Abstract: Pancreatitis-associated ascitic fluid up-regulated proinflammatory cytokines by interfering with proinflammatory and anti-inflammatory signaling pathways, thus exacerbating activation in acute pancreatitis.

Cited by 15 publications

References 27 publications

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Astragalusmembranaceusmodulates Th1/2 immune balance and activates PPARγ in a murine asthma model

Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis

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