NLRP3 Inflammasome-Mediated Inflammation in Acute Pancreatitis

Ferrero-Andrés, Ana; Panisello‐Roselló, Arnau; Roselló‐Catafau, Joan; Folch-Puy, Emma

doi:10.3390/ijms21155386

Cited by 47 publications

(32 citation statements)

References 148 publications

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“…NF- κ B is the subject of much active research among pharmaceutical companies as a target for anti-cancer therapy 67 . Abnormal expressions of NFKB1 and RELA are mediated through mRNA modifications 68 . The recent progress in N4- Acetylcytidine (N4A) on RNA expression is also playing key role on the cancer development 69 .…”

Section: Discussionmentioning

confidence: 99%

PCA-based unsupervised feature extraction for gene expression analysis of COVID-19 patients

Fujisawa

Shimo

Taguchi

et al. 2021

Sci Rep

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Coronavirus disease 2019 (COVID-19) is raging worldwide. This potentially fatal infectious disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the complete mechanism of COVID-19 is not well understood. Therefore, we analyzed gene expression profiles of COVID-19 patients to identify disease-related genes through an innovative machine learning method that enables a data-driven strategy for gene selection from a data set with a small number of samples and many candidates. Principal-component-analysis-based unsupervised feature extraction (PCAUFE) was applied to the RNA expression profiles of 16 COVID-19 patients and 18 healthy control subjects. The results identified 123 genes as critical for COVID-19 progression from 60,683 candidate probes, including immune-related genes. The 123 genes were enriched in binding sites for transcription factors NFKB1 and RELA, which are involved in various biological phenomena such as immune response and cell survival: the primary mediator of canonical nuclear factor-kappa B (NF-κB) activity is the heterodimer RelA-p50. The genes were also enriched in histone modification H3K36me3, and they largely overlapped the target genes of NFKB1 and RELA. We found that the overlapping genes were downregulated in COVID-19 patients. These results suggest that canonical NF-κB activity was suppressed by H3K36me3 in COVID-19 patient blood.

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Section: Discussionmentioning

confidence: 99%

PCA-based unsupervised feature extraction for gene expression analysis of COVID-19 patients

Fujisawa

Shimo

Taguchi

et al. 2021

Sci Rep

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“…It is supposed that the mechanism by which Mito-TEMPO produced anti-inflammatory effects maybe by the prevention of mitochondrial reactive oxygen species that were involved in activation of TLR-4 and hence NF-кB signaling and this will lead to prevention of NLRP3 inflammasome activation and hence caspase-1 and its related cytokines like IL-1β and IL-18 [49][50][51] .…”

Section: Discussionmentioning

confidence: 99%

Mito-TEMPO improved L-Arginine- induced acute pancreatitis in rats via TLR-4/ NF-кB/ NLRP3 inflammasome downregulation and antioxidant properties

Fawzy

Fikry

Fawzy

et al. 2021

Azhar International Journal of Pharmaceutical and Medical Scien

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Background: Acute pancreatitis (AP) is a globally significant disease with increasing incidence and prevalence especially in the western world. It has severe complications such as pseudocyst, infection, renal failure, breathing problems, diabetes, malnutrition and chronic pancreatitis. Chronic pancreatitis can lead to pancreatic cancer which is one of the worst types of cancer. Up till now, there is no licensed specific treatment for AP. Objective: This study investigated the therapeutic effects of Mito-TEMPO in the treatment of L-Arginine induced acute pancreatitis in rats besides a possible involved mechanistic pathway. Materials and Methods: Rats randomly allocated into 3 groups: (1) control (received normal saline), (2) L-Arginine treated (300mg/100gm, i.p once) & (3) L-Arginine+Mito-TEMPO treated (0.7mg/kg/ day, i.p for 7 days). After 7 days from AP induction, serum amylase & lipase, pancreatic inflammatory mediators "toll-like receptor-4 (TLR-4), nuclear factor kappa-B (NF-кB), NLRP3 inflammasome, caspase-1, interleukin-1 beta (IL-1B)", oxidative parameters "malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), reduced glutathione (GSH)", an apoptotic marker "caspase-3" & pancreatic histopathological changes were estimated for all rats.Results: L-Arginine induced AP was evidenced by elevation of serum amylase & lipase, pancreatic inflammatory mediators "TLR-4, NF-кB, NLRP3 inflammasome, caspase-1, IL-1B", oxidative parameters "MDA, MPO, NO", the apoptotic marker "caspase-3" and infiltration of inflammatory cells proved through hematoxylin & eosin stain alongside with the reduction of GSH content. All these harmful effects were improved significantly after the administration of Mito-TEMPO. Conclusion: Mito-TEMPO can be introduced as a new therapy for the treatment of acute pancreatitis due to its anti-inflammatory and antioxidant effects.

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“…5 When the activation pathway of inflammasome is inhibited, the mortality of pancreatic cells decreases significantly, which indicates that pyroptosis plays an important role in the development of pancreatitis. 14 Most scholars believe that pyroptosis can aggravate inflammatory reaction. For example, Mazzolini's study on liver inflammation found that pyroptosis aggravated the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Study on the inhibitory effect of ulinastatin on caspase-1-dependent pyroptosis in acinar cells of acute pancreatitis

Guo

Wang

et al. 2021

Eur J Inflamm

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Objectives Pyroptosis, a special kind of cell death, is generally believed to aggravate the inflammatory response. It has been found that the acinar cell pyroptosis exits in the course of pancreatitis. Ulinastatin has the function of inhibiting the release of inflammatory mediators, thereby reducing the inflammatory reaction, which suggests that ulinastatin has potential inhibitory effect on pyroptosis. The aim of this study is to investigate the effect of ulinastatin on caspase-1-dependent acinar cell pyroptosis in acute pancreatitis. Methods Acute pancreatitis model was established by intraperitoneal injection of L-arginine. Rats in ulinastatin group were injected with ulinastatin intravenously after successful modeling. The pancreatic tissues of rats were subjected to pathological examination and detection of cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18. Serum samples were also collected for measurement of IL-1β, IL-18, amylase, and lipase. Results Slight pathological damage of pancreas was observed in the pancreatitis and the ulinastatin group. Compared with the blank control group ( p < .05), the protein levels of cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18 were significantly increased in pancreatitis group but decreased in ulinastatin group ( p < .05). The positive reaction of caspase-1 in pancreatitis group was significantly higher than that in the blank control group ( p < .05). After administration of ulinastatin, the positive reaction of caspase-1 was significantly lower than that in pancreatitis group ( p < .05). As for the levels of serum IL-1β and IL-18, they were significantly higher in pancreatitis group than those in the blank control group ( p < .05). Administration of ulinastatin significantly decreased the serum levels of IL-1β and IL-18 ( p < .05). And the serum amylase and lipase levels elevated in pancreatitis group, while significantly inhibited by ulinastatin ( p < .05). Conclusions The results showed that the onset of acute pancreatitis was accompanied by obvious acinar cell pyroptosis. Ulinastatin could inhibit caspase-1-dependent acinar cell pyroptosis in acute pancreatitis.

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NLRP3 Inflammasome-Mediated Inflammation in Acute Pancreatitis

Cited by 47 publications

References 148 publications

PCA-based unsupervised feature extraction for gene expression analysis of COVID-19 patients

PCA-based unsupervised feature extraction for gene expression analysis of COVID-19 patients

Mito-TEMPO improved L-Arginine- induced acute pancreatitis in rats via TLR-4/ NF-кB/ NLRP3 inflammasome downregulation and antioxidant properties

Study on the inhibitory effect of ulinastatin on caspase-1-dependent pyroptosis in acinar cells of acute pancreatitis

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