The Role of Toll-Like Receptor Polymorphisms in Acute Pancreatitis Occurrence and Severity

Matas-Cobos, Ana M; Redondo–Cerezo, Eduardo; Alegría-Motte, Carlos; Martínez-Chamorro, Alba; Sáenz-López, Pablo; Jiménez, Pilar; Ruiz-Cabello, Francisco; González-Calvin, Jorge L.; Teresa, J. De; Osuna, Francisco Ruiz-Cabello

doi:10.1097/mpa.0000000000000272

Cited by 27 publications

(14 citation statements)

References 37 publications

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“…previous study indicated that serum amylase is always high in AP (30). Matas-Cobos reported increased serum amylase levels in AP, which was consistent with the present study (31). Therefore, the results indicated that DUSP1 gene silencing upregulated the expression of proinflammatory cytokines, HMGB1, S100A12 and amylase.…”

Section: Discussionsupporting

confidence: 92%

Effects of silencing the DUSP1 gene using lentiviral vector-mediated siRNA on the release of proinflammatory cytokines through regulation of the MAPK signaling pathway in mice with acute pancreatitis

Zhang

Xie

et al. 2018

Int J Mol Med

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The present study investigated the effects of dual specificity phosphatase 1 (DUSP1) gene silencing using lentiviral vector-mediated small interfering (si)RNA on the release of proinflammatory cytokines through the regulation of the mitogen‑activated protein kinase (MAPK) signaling pathway in mice with acute pancreatitis (AP). Two siRNA‑DUSP1 sequences and one scramble siRNA sequence were designed, and the expression of DUSP1 was detected using western blot analysis to screen for the one with a higher interference rate. An AP mouse model was established, and KM mice were assigned to either a control, siRNA, AP, AP+PD98059, AP+scramble, AP+siRNA or AP+PD98059+siRNA group. The expression of proinflammatory cytokines, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6, high mobility group box 1 (HMGB1), and S100A12 in serum samples were detected using an enzyme‑linked immunosorbent assay at 12, 24 and 48 h post‑modeling. The serum amylase levels were also detected. The expression levels of DUSP1, TNF‑α, IL‑1β, IL‑6, HMGB1, S100A12, phosphorylated (p‑) extracellular signal‑regulated kinase (ERK), p‑c‑Jun N‑terminal kinase (JNK), p‑p38, ERK, JNK and p38 in pancreatic, liver, kidney and lung tissues were detected using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Compared with the control group, the siRNA group demonstrated marginally upregulated serum amylase, lipase, urinary trypsinogen‑2, and proinflammatory cytokines, HMGB1 and S100A12 in serum and tissues, with no statistically significant difference, elevated expression levels of p‑ERK, p‑JNK and p‑p38, and decreased expression of DUSP1. The other five groups demonstrated increased expression levels of TNF‑α, IL‑1β, IL‑6, HMGB1, S100A12, amylase, lipase and urinary trypsinogen‑2 in serum, and increased expression levels of DUSP1, TNF‑α, IL‑1β, IL‑6, HMGB1, S100A12, p‑ERK, p‑JNK and p‑p38 in tissues. Compared with the AP group, the AP+PD98059+siRNA group had decreased expression of DUSP1 in tissues, whereas the AP+PD98059 group had decreased serum expression levels of TNF‑α, IL‑1β, IL‑6, HMGB1, S100A12 and amylase, lipase and urinary trypsinogen‑2. The expression levels of TNF‑α, IL‑1β, IL‑6, HMGB1, S100A12, p‑ERK, p‑JNK, p‑p38 in tissues, and edema of pancreatic tissue were alleviated, whereas the opposite results were observed in the AP+siRNA group with the decreased expression of DUSP1. The results suggested that DUSP1 gene silencing promoted the release of proinflammatory cytokines through activation of the MAPK signaling pathway in mice with AP.

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Section: Discussionsupporting

confidence: 92%

Effects of silencing the DUSP1 gene using lentiviral vector-mediated siRNA on the release of proinflammatory cytokines through regulation of the MAPK signaling pathway in mice with acute pancreatitis

Zhang

Xie

et al. 2018

Int J Mol Med

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“…It has been suggested that many lifestyle choices and environmental factors such as excessive drinking, pancreatic duct strictures, viral or bacterial infection, hyperlipidemia, metabolic disorders, and infections are associated with disease susceptibility (Álvarez et al, 2015;Greer et al, 2015;Pohl and Uc, 2015;Talukdar and Vege, 2015;Tun-Abraham et al, 2015). Recent studies have reported that genetic factors play an important role in the pathogenesis of acute pancreatitis, such as interleukin-1β (IL-1β), IL-8, IL-10, heme oxygenase-1 gene, Toll-like receptor gene, tumor necrosis factor alpha gene, and heat-shock protein 70-2 gene (Özhan et al, 2010;Bishehsari et al, 2012;Srivastava et al, 2012;Gulla et al, 2014;Li et al, 2015;Matas-Cobos et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Role of IL-10 gene polymorphisms in the development of acute pancreatitis

Tang

Hou

et al. 2016

Genet. Mol. Res.

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“…Many authors observed a significant association of the synonymous variant c.180C > T (p.G60=) with CP [7, 16, 18, 19]. In the Indian studies, the variant c.180C > T (p.G60=) was found in 23–29% of the subject population.…”

Section: Discussionmentioning

confidence: 99%

CTRC gene polymorphism (p.G60=; c.180 C > T) in acute pancreatitis

et al. 2017

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BackgroundThe aim of the study was to determine the relationship between the presence of p.G60 = polymorphism (c.180C > T; rs497078) CTRC and the incidence together with the clinical course of acute pancreatitis (AP).MethodsTwo hundred ninety-nine people suffering from AP and 417 healthy volunteers were subjected to the study. DNA was isolated from blood samples.Results CTRC p.G60 = polymorphism (c.180C > T) occurred more frequently in the AP group (p = 0.015). The CT and TT genotype was found in 27.8% of the AP patients and in 19.9% of the healthy subjects (p = 0.017). No significant correlation was found between having the CT and TT genotype and the severity of the AP clinical course. In 6 patients (2%) with the CT genotype, a SPINK1 gene mutation was found, while in the control group it was found in 3 patients (0.7%), (p > 0.05). All patients with the present SPINK1 mutation with the CT genotype had a moderate or a severe course of the disease (p = 0.0007).Conclusions CTRC polymorphism Hetero p.G60=; c.180C > T increases the risk of an AP occurrence and together with the SPINK 1 mutation, may be responsible for a more severe course of the disease.

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The Role of Toll-Like Receptor Polymorphisms in Acute Pancreatitis Occurrence and Severity

Abstract: Our article points to genetic polymorphisms in TLR3 and TLR6 as having a plausible role in the occurrence of severe AP.

Cited by 27 publications

References 37 publications

Effects of silencing the DUSP1 gene using lentiviral vector-mediated siRNA on the release of proinflammatory cytokines through regulation of the MAPK signaling pathway in mice with acute pancreatitis

Effects of silencing the DUSP1 gene using lentiviral vector-mediated siRNA on the release of proinflammatory cytokines through regulation of the MAPK signaling pathway in mice with acute pancreatitis

Role of IL-10 gene polymorphisms in the development of acute pancreatitis

CTRC gene polymorphism (p.G60=; c.180 C > T) in acute pancreatitis

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