p38 MAPK inhibition alleviates experimental acute pancreatitis in mice

Cao, Mingtao; Xu, Jing; Cai, Haidong; Lv, Zhongwei; Feng, Yuheng; Li, Kun; Chen, Chunqiu; Li, Yongyu

doi:10.1016/s1499-3872(15)60327-7

Cited by 27 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study identified that the activation of MAPK is associated with the upregulation of gene expression involved in the proliferation and apoptosis of pancreatic cancer cells (33). The p38 MAPK signaling pathway can function as a regulator of the inflammatory response, and inhibition of the p38 MAPK signaling pathway can alleviate experimental AP in mice (34). A study by Sun et al also demonstrated that inhibition of the MAPK signaling pathway decreased the mRNA expression of proinflammatory cytokines (35).…”

Section: Discussionmentioning

confidence: 98%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 98%

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

View full text Add to dashboard Cite

show abstract

“…A previous study reported that p38 MAPK is associated with the severity of pancreatitis and in the respiratory distress syndrome associated with acute pancreatitis ( 34 ). Another study using pancreatic fragments stimulated by the cholecystokinin analog, cerulein, demonstrated that proinflammatory mediator production was increased in parallel with the activation of p38 MAPK, and that these alterations were attenuated by treatment with chemical inhibitors of p38 MAPK ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin

Deng

Abliz

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Recent studies demonstrated that apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor, significantly decreased acute pancreatitis-associated inflammatory and oxidative stress parameters. In addition, apocynin was able to reduce ischemic reperfusion injury-associated damage; however, the exact effects of apocynin on acute pancreatitis-associated intestinal mucosal injury have yet to be fully clarified. The present study aimed to investigate the protective effects of apocynin on intestinal mucosal injury in a rat model of severe acute pancreatitis (SAP). A total of 60 male Sprague Dawley rats were randomly divided into four groups (n=15/group): Sham operation group (SO), SAP group, apocynin treatment (APO) group and drug control (APO-CON) group. SAP was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Apocynin was administered 30 min prior to SAP induction in the APO group. All rats were sacrificed 12 h after SAP induction. Intestinal integrity was assessed by measuring diamine oxidase (DAO) levels. Morphological alterations to intestinal tissue were determined under light and transmission electron microscopy. NOX2, p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB expression levels were detected in the intestine by immunohistochemical staining. Oxidative stress was detected by measuring intestinal malondialdehyde (MDA) and superoxide dismutase content. In addition, blood inflammatory cytokines, and amylase (AMY) and lipase (LIP) levels were evaluated. The results demonstrated that apocynin attenuated the following: i) Serum AMY, LIP and DAO levels; ii) pancreatic and intestinal pathological injury; iii) intestinal MDA content; iv) intestinal ultrastructural alterations; v) serum interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels; and vi) NOX2, p38 MAPK and NF-κB expression in intestinal tissues. These results suggested that apocynin may attenuate intestinal barrier dysfunction in sodium taurocholate-induced SAP, presumably via its role in the prevention of reactive oxygen species generation and inhibition of p38 MAPK and NF-κB pathway activation. These findings provide novel insight suggesting that pharmacological inhibition of NOX by apocynin may be considered a novel therapeutic method for the treatment of intestinal injury in SAP.

show abstract

“…MAPK was an important transmitter of signals from the cell surface to the inside of the nucleus and MAPK 3 acted as an essential component of the MAPK signal transduction pathway [25]. The MAPK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements [26]. It had been reported that pancreatitis could be alleviated via reducing the production of TNF-α, IL-6, IL-1β which was associated with regulating the MAPK signaling way [27].…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Pharmacological of Xiaochaihu Decoction in the Treatment of Pancreatitis Based on the Network Pharmacology

Zhan

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundXiaochaihu Decoction (XD) was a traditional prescription, has been demonstrated the pharmacodynamic on pancreatitis. But the underline mechanism remained to be explored. Therefore, this study was aimed to combined network pharmacology method and molecular docking technology to demonstrate the potential mechanism of XD treated with pancreatitis.MethodsFirstly, compounds of seven herbs containing XD were collected from TCMSP Database and the putative targets of Pancreatitis were obtained from OMIM, TTD, Genecards Database. Then PPI network was constructed according to the matching results between XD potential targets and pancreatic neoplasms targets. Furthermore, enrichment analysis on GO and KEGG by DAVID utilized bioinformatics resources. Finally, Molecular Docking was performed to simulate the interaction between the active compound of XD and putative targets.ResultsA total of 196 active ingredients and 91 putative targets were selected out. The PPI interaction network analysis demonstrated that Quercetin was the candidate agents and MAPK3, IL-6 and TP53 were the potential targets for the XD treatment of pancreatitis. The KEGG analysis revealed that pathways in cancers, TNF signaling way, MAPK signaling way might play an important role in pancreatitis therapy. And Molecular Docking results showed that Quercetin combined well with MAPK3, IL-6 and TP53.ConclusionThis study illustrated that Quercetin containing in XD might played an important role in pancreatitis therapy by acting the key genes of MPAK3, IL-6 and TP53. And it also provided a strategy to elucidate the mechanisms of Traditional Chinese Medicine (TCM) at the level of network pharmacology.

show abstract

p38 MAPK inhibition alleviates experimental acute pancreatitis in mice

Cited by 27 publications

References 29 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

Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin

Uncovering the Pharmacological of Xiaochaihu Decoction in the Treatment of Pancreatitis Based on the Network Pharmacology

Contact Info

Product

Resources

About