Involvement of Nucleotide-Binding and Oligomerization Domain-Like Receptors in the Intestinal Injury of Severe Acute Pancreatitis in Rats

Xu, Shangcheng; Wei, Shuqing; Guo, Yu; Cui, Dong-Lai; Yao, Jiang

doi:10.1097/mpa.0000000000000977

Cited by 10 publications

(10 citation statements)

References 22 publications

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“…Studies focusing on TLRs, such as the interaction between TLR4 and lipopolysaccharide (LPS), have established a well-known link between the microbiota and the host (Sharif et al, 2009;Cao et al, 2018). Recently, other cytosolic receptor NLRs have attracted increasing attention for their significant role in inflammation and immunity, especially in SAP (Clarke et al, 2010;Xu et al, 2018). Tsuji et al showed that NOD1 activation in acinar cells by gut microbiota played an indispensable role in the occurrence of cerulein-induced AP (Tsuji et al, 2012), where diaminopimelic acid (DAP) from cell wall peptidoglycans of gram-negative bacteria and particular gram-positive bacteria is a ligand for NOD1 that can induce innate immune responses.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis

Jiao

et al. 2022

Front. Cell. Infect. Microbiol.

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Impaired intestinal barrier function and gut microbiota dysbiosis are believed to be related to exacerbation of acute pancreatitis (AP). As a bacterial cell wall peptidoglycan component, diaminopimelic acid (DAP) is a specific ligand of NOD1 that regulates the NOD1/RIP2/NF-kB signaling pathway. Here, we investigated the role of DAP in the crosstalk between the gut microbiota and pancreas during the occurrence of AP. Upregulation of NOD1/RIP2/NF-kB and elevated serum DAP levels were found in severe AP (SAP) model rats. The accumulation of DAP in SAP patients corroborated its ability to serve as an indicator of disease severity. Subsequently, SAP rats were treated with oral administration of the traditional Chinese medicine Qingyi Keli (QYKL) as well as neomycin, which can widely eliminate DAP-containing bacteria. Both QYKL and neomycin intervention ameliorated intestinal and pancreatic damage and systemic inflammation in SAP rats. Through 16S rDNA sequencing, we found that QYKL could rehabilitate the gut microbiota structure and selectively inhibit the overgrowth of enteric bacteria, such as Helicobacter and Lactobacillus, in SAP rats without affecting some protective strains, including Romboutsia and Allobaculum. Interestingly, we demonstrated that the decrease in serum DAP was accompanied by suppression of the NOD1/RIP2/NF-kB signaling pathway in both the intestine and pancreas of the two intervention groups. Taken together, these results suggested that the gut microbiota-DAP-NOD1/RIP2 signaling pathway might play a critical role in the progression of AP and that SAP could be alleviated via intervention in the signaling pathway. Our work provides new potential early warning indicators of SAP and targets for intervention.

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Section: Introductionmentioning

confidence: 99%

Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis

Jiao

et al. 2022

Front. Cell. Infect. Microbiol.

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“…intestinal bacterial translocation; however, its pathogenesis has yet to be fully studied. [1][2][3][4] Studies have found that the leading causes of death are secondary bacterial infections after pancreatic tissue necrosis in SAP, subsequent systemic inflammatory response syndrome, and multiple organ failure. [2][3][4] Related experimental studies have confirmed that the bacterial infection of SAP is caused by intestinal bacterial translocation attributed to the SAP-induced destruction of the intestinal mucosal barrier.…”

Section: Effects Of Emodin On Intestinal Mucosal Barrier By the Upregulation Of Mir-218a-5p Expression In Rats With Acute Necrotizing Panmentioning

confidence: 99%

“… 1 SAP may be related to the mechanisms of self-digestion of the pancreas, the cascade of inflammatory mediators caused by pancreatic tissue damage, pancreatic blood circulation disorder induced by inflammatory mediators and vasoactive substances, and secondary infection of the pancreas due to intestinal bacterial translocation; however, its pathogenesis has yet to be fully studied. 1 – 4 Studies have found that the leading causes of death are secondary bacterial infections after pancreatic tissue necrosis in SAP, subsequent systemic inflammatory response syndrome, and multiple organ failure. 2 – 4 Related experimental studies have confirmed that the bacterial infection of SAP is caused by intestinal bacterial translocation attributed to the SAP-induced destruction of the intestinal mucosal barrier.…”

Section: Introductionmentioning

confidence: 99%

“… 1 – 4 Studies have found that the leading causes of death are secondary bacterial infections after pancreatic tissue necrosis in SAP, subsequent systemic inflammatory response syndrome, and multiple organ failure. 2 – 4 Related experimental studies have confirmed that the bacterial infection of SAP is caused by intestinal bacterial translocation attributed to the SAP-induced destruction of the intestinal mucosal barrier. 5 Therefore, enhancing the regeneration of the intestinal mucosal epithelium and repair, maintaining the integrity of the intestinal mucosal barrier, enhancing the intestinal immune function, and reducing the release of inflammatory mediators and cytokines 4 , 5 can improve the prognosis of patients with SAP.…”

Section: Introductionmentioning

confidence: 99%

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Effects of emodin on intestinal mucosal barrier by the upregulation of miR-218a-5p expression in rats with acute necrotizing pancreatitis

Tan

Zhang

et al. 2020

Int J Immunopathol Pharmacol

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Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3, and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.

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“…However, longterm total parenteral nutrition (TPN) can precipitate intestinal barrier dysfunction and induce or aggravate systemic inflammatory responses and multiple organ dysfunction. In recent years, early enteral nutrition (EEN) was demonstrated to play a significant role in protecting the integrity of intestinal mucosal structures and functions, alleviating systemic inflammatory response, and preventing shifts in bacterial populations (Xu et al, 2018;Zhang et al, 2018). In addition, EEN can alleviate augmented immune responses in the early stages of SAP, thus avoiding the emergence of immunosuppression (Sun et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Luzhou‐Feier powder reduces inflammatory response and improves intestinal immune barrier in rats with severe acute pancreatitis

et al. 2021

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Involvement of Nucleotide-Binding and Oligomerization Domain-Like Receptors in the Intestinal Injury of Severe Acute Pancreatitis in Rats

Abstract: The NLRs, including NOD1, NOD2, and NLRP3, were involved in the intestinal injury in SAP through a caspase-1 pathway.

Cited by 10 publications

References 22 publications

Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis

Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis

Effects of emodin on intestinal mucosal barrier by the upregulation of miR-218a-5p expression in rats with acute necrotizing pancreatitis

Luzhou‐Feier powder reduces inflammatory response and improves intestinal immune barrier in rats with severe acute pancreatitis

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