CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9‐dependent NF‐κB and P38MAPKs pathway

Yang, Zhiwen; Meng, Xiaoxiao; Zhang, Chun; Xu, Ping

doi:10.1111/jcmm.13040

Cited by 19 publications

(31 citation statements)

References 29 publications

(42 reference statements)

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“…Blocking the activation of NF- κ B appears to reduce the inflammatory response in SAP [21]. TNF- α is a multifunctional proinflammatory cytokine and is significantly correlated with the expression of NF- κ B [22].…”

Section: Introductionmentioning

confidence: 99%

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Piao¹,

Liu

Guo

et al. 2017

Oxidative Medicine and Cellular Longevity

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Picroside II, from the herb Picrorhiza scrophulariiflora Pennell, has antioxidant and anti-inflammatory activities. However, its function on severe acute pancreatitis (SAP) and molecular mechanism remains unknown. The effects of picroside II on the SAP induced by cerulean were investigated. SAP rats were treated with picroside II (25 mg/kg). The severity of SAP was evaluated by using biochemical and histological analyses. Pancreatic cancer cell PANC-1 was transfected with ptfLC3 (an indicator of autophagic activity), pcDNA3.1-NF-κB (nuclear factor kappa B), and pTZU6+1-NF-κB-shRNA and then treated with picroside II. Relative molecules related with NF-κB-dependent autophagy were detected by using Western blot. Autophagic activities were observed by phase-contrast and fluorescent microscopes. Acetylated LC3 was detected by immunoprecipitation. The results showed that picroside II treatment reduced the level of ALT, AST, NF-κB, IL-1β, IL-6, TNF-α, and SIRT1 (NAD+-dependent deacetylase) and increased the level of SOD and GSH. The autophagic activity was reduced when NF-κB was silenced, and the levels of TNF-α and SIRT1 were reduced. In contrast, the overexpression of NF-κB increased autophagic activity and the level of TNF-α, which activated SIRT1. SIRT1 deacetylated LC3 and increased autophagic activities. Picroside II ameliorates SAP by improving antioxidant and anti-inflammtory activities of SAP models via NF-κB-dependent autophagy.

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Section: Introductionmentioning

confidence: 99%

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Piao¹,

Liu

Guo

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…To further explore the mechanisms that underlie reduced pancreatic injury after Ad-FGL2-miRNA administration, we evaluated the expression of the cytokines TNF-α and IL-1β by real-time PCR and ELISA. These cytokines play important roles in the development of SAP [ 4 ]. As shown in Figure 5 , concentrations of these cytokines were similar in SO group.…”

Section: Resultsmentioning

confidence: 99%

“…The TLR4 and p38 MAPK protein have been shown to play a pivotal role in the development of SAP, inducing the release of several inflammatory cytokines [ 4 ]. To investigate the role that FGL2 up-regulation plays in TLR4 and p38 MAPK activation, Ad-FGL2-miRNA was applied to deplete FGL2 expression in SAP mice.…”

Section: Resultsmentioning

confidence: 99%

“…In the recent years, accumulating studies have provided strong evidence in supporting a pivotal role of toll-like receptor 4 (TLR4) and p38 mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of SAP [ 4 – 6 ]. TLR4 is a kind of inflammatory transmembrane receptor that is expressed by epithelia in pancreatic ducts and acinus.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus-mediated artificial miRNA targetting fibrinogen-like protein 2 attenuates the severity of acute pancreatitis in mice

Ding

Chen

et al. 2017

Bioscience Reports

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Severe acute pancreatitis (SAP) remains to be challenging for its unpredictable inflammatory progression from acute pancreatitis to SAP. Apoptosis is an important pathology of SAP. Fibrinogen-like protein 2 (FGL2) has been reported to be involved in apoptosis. The present study aimed to explore the therapeutic effect of an adenovirus-mediated artificial miRNA targetting FGL2 (Ad-FGL2-miRNA) in taurocholate-induced murine pancreatitis models. Sodium taurocholate was retrogradely injected into the biliopancreatic ducts of the C57/BL mice to induce SAP. FGL2 expression was measured with reverse transcription-PCR, Western blotting, and immunohistochemical staining. ELISA was used to detect the activity of amylase and the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In addition, the mRNA levels of TNF-α and IL-1β were also detected. Finally, apoptosis was assessed by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) method and Western blotting. Ad-FGL2-miRNA significantly suppressed FGL2 expression and alleviated pancreatic injury. Also, Ad-FGL2-miRNA markedly inhibited a post-SAP increase in the activation of TNF-α and IL-1β. Finally, pretreatment with Ad-FGL2-miRNA ameliorated apoptosis at the early stage of SAP by modulating cleaved caspase-3 and therefore played a protective role. These results indicated that FGL2 might be a promising target for attenuating the severity of SAP and adenovirus-mediated artificial miRNAs targetting FGL2 represented a potential therapeutic approach for the treatment of SAP.

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“…It has been reported that the levels of interleukin (IL)-1β, IL-6 and TNF-α in the serum of SAP patients were significantly increased, indicating that a systemic inflammatory response serves a critical role in the progression of SAP (12,13). The pathogenesis of SAP may be associated with excessive activation of the NF-κB signaling pathway, leading to a large number of inflammatory mediators (14,15). Once the cytokines are produced, they not only activate themselves, but also promote the production of other cytokines, causing interlocking and amplification effects that impair the structure and function of the pancreas (16).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory stimuli promote oxidative stress in pancreatic acinar cells via Toll-like receptor 4/nuclear factor-κB pathway

Pan

Wang

et al. 2018

Int J Mol Med

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The Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway is vital to the pathogenesis of acute pancreatitis (AP). The aim of the present study was to identify the mechanism of the activation of the TLR4/NF-κB signaling pathway in the viability of primary pancreatic cells. The cells were stimulated with lipopolysaccharide (LPS) for the activation of NF-κB signaling. Next, the reactive oxygen species (ROS) level was evaluated by detecting the concentration of malondialdehyde and glutathione peroxidase. cell viability was measured by cell counting Kit-8 and MTT assays, while the percentage of apoptosis was detected by flow cytometry. Quantitative polymerase chain reaction was used to detect TLR4, B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax) and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) expression levels. Western blot assay was also conducted to detect TLR4 protein expression, while the activity of NF-κB signaling was measured by determining the p65 and phosphorylated p65 protein levels. In addition, the effect of TLR4 overexpression or treatment with TLR4 antagonists in the presence of LPS stimulation was investigated. The results revealed that ROS levels were increased and cell viability was decreased in LPS-stimulated pancreatic acinar cells. TLR4, Bax and PMAIP1 levels were increased, Bcl2 expression was decreased and NF-κB signaling was activated in LPS-stimulated pancreatic acinar cells. Furthermore, pancreatic cells with TLR4 overexpression exhibited increased ROS level and decreased viability. Finally, the effect caused by LPS stimulation was partially reversed by treatment of pancreatic acinar cells with TLR4 antagonists. In conclusion, the current study investigated a novel regulatory mechanism of the TLR4/NF-κB pathway in LPS-stimulated pancreatic cells, which may contribute to pancreatitis. The damage of these cells due to increased ROS levels was observed to occur through activation of the TLR4/NF-κB pathway.

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CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9‐dependent NF‐κB and P38MAPKs pathway

Cited by 19 publications

References 29 publications

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Adenovirus-mediated artificial miRNA targetting fibrinogen-like protein 2 attenuates the severity of acute pancreatitis in mice

Inflammatory stimuli promote oxidative stress in pancreatic acinar cells via Toll-like receptor 4/nuclear factor-κB pathway

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