β‐Arrestin1 alleviates acute pancreatitis via repression of NF‐κBp65 activation

Li, Tao; Lin, Xiao; Tan, Siwei; Lei, Yiming; Liu, Huiling; Guo, Yuwei; Fang, Zheng; Wu, Bin

doi:10.1111/jgh.14450

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…Actually, existing studies have reported that ARRB1 not only responds to the termination of G-protein activation as a classic adaptor protein but also participates in the mediation of the inflammatory response through multiple signal transduction pathways. Preceding research from our team revealed that ARRB1 alleviated acute pancreatitis via repression of NF-κBp65 activation [ 27 ]. A recent study showed that ARRB1 inhibited nonalcoholic steatohepatitis progression by promoting growth differentiation factor 15 maturation [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

et al. 2021

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Acute liver injury (ALI) caused by multiple inflammatory responses is a monocyte-/macrophage-mediated liver injury that is associated with high morbidity and mortality. Liver macrophage activation is a vital event that triggers ALI. However, the mechanism of liver macrophage activation has not been fully elucidated. This study examined the role of β-arrestin1 (ARRB1) in wild-type (WT) and ARRB1-knockout (ARRB1-KO) mouse models of ALI induced by lipopolysaccharide (LPS), and ARRB1-KO mice exhibited more severe inflammatory injury and liver macrophage activation compared to WT mice. We found that LPS treatment reduced the expression level of ARRB1 in Raw264.7 and THP-1 cell lines, and mouse primary hepatic macrophages. Overexpression of ARRB1 in Raw264.7 and THP-1 cell lines significantly attenuated LPS-induced liver macrophage activation, such as transformation in cell morphology and enhanced expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), while downregulation of ARRB1 by small interfering RNA and ARRB1 deficiency in primary hepatic macrophages both aggravated macrophage activation. Moreover, overexpression of ARRB1 suppressed LPS-induced endoplasmic reticulum (ER) stress in liver macrophages, and inhibition of ER stress impeded excessive hepatic macrophage activation induced by downregulation of ARRB1. Our data demonstrate that ARRB1 relieves LPS-induced ALI through the ER stress pathway to regulate hepatic macrophage activation and that ARRB1 may be a potential therapeutic target for ALI.

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Section: Discussionmentioning

confidence: 99%

ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

et al. 2021

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“…Relative mRNA expression was normalized to the mRNA levels of β-actin (housekeeping control). 21,31–36 Detailed primer sequences are shown in Table 2.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoreactivity was analysed using Western Lightening Plus enhanced chemiluminescence (PerkinElmer, MA, USA) according to the manufacturer's instructions. GAPDH was adopted as internal standard to control for unwanted sources of variation, and relative protein expression values were expressed as 'fold mean of the controls' by comparing with the corresponding control value, 32,[37][38][39][40] and the control value was normalized to 1.0.…”

Section: Western Blot Analysismentioning

confidence: 99%

Combinatory antibiotic treatment protects against experimental acute pancreatitis by suppressing gut bacterial translocation to pancreas and inhibiting NLRP3 inflammasome pathway

et al. 2019

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Gut bacterial translocation following impaired gut barrier is a critical determinant of initiating and aggravating acute pancreatitis (AP). Antibiotic combination (ABX; vancomycin, neomycin and polymyxin b) is capable of reducing gut bacteria, but its efficacy in AP prevention and the underlying mechanism have not been investigated yet. AP was induced in BALB/c mice by caerulein (CAE) hyperstimulation. We found that ABX supplementation attenuated the severity of AP as evidenced by reduced pancreatic oedema and myeloperoxidase activity. The protective effect was also confirmed by improved histological morphology of the pancreas and decreased pro-inﬂammatory markers (IL-1β, TNF-α, MCP-1) in pancreas. ABX administration inhibits the activation of colonic TLR4/NLRP3 inflammasome pathway. Subsequently, down-regulated NLRP3 resulted in decreased colonic pro-inflammation (IL-1β, IL-6, MCP-1) and enhanced gut physical barrier as evidenced by up-regulation of tight junction proteins including occludin, claudin-1 and ZO-1, as well as improved histological morphology of the colon. Together, combinatory ABX therapy inhibited the translocation of gut bacteria to pancreas and its amplification effects on pancreatic inflammation by inhibiting the pancreatic NLRP3 pathway, and inhibiting intestinal-pancreatic inflammatory responses. The current study provides the basis for potential clinical application of ABX in AP.

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“…It has been demonstrated that nearly all pathways leading to NF-κB activation could be blocked by treatment with a variety of antioxidants, including N-acetyl-L-cysteine (NAC), glutathione (GSH), and thioredoxin (Mercurio & Manning, 1999 ). In recent years, a large number of active drugs have emerged to improve therapy for acute pancreatitis by inhibiting the NF-κB signaling pathway in experiments (Cen et al., 2016 ; Tao et al., 2019 ). Bilirubin is a bioproduct, and possessed potent antioxidant and anti-inflammatory properties (Yao, Jiang, et al., 2019 ; Yao, Jiang, 2019 ; Yao, Huang, 2020 ; Yao, Sun, 2020 ).…”

Section: Molecular and Cellular Mechanisms Of Acute Pancreatitismentioning

confidence: 99%

Drug discovery and formulation development for acute pancreatitis

et al. 2020

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Acute pancreatitis is a sudden inflammation and only last for a short time, but might lead to a life-threatening emergency. Traditional drug therapy is an essential supportive method for acute pancreatitis treatment, yet, failed to achieve satisfactory therapeutic outcomes. To date, it is still challenging to develop therapeutic medicine to redress the intricate microenvironment promptly in the inflamed pancreas, and more importantly, avoid multi-organ failure. The understanding of the acute pancreatitis, including the causes, mechanism, and severity judgment, could help the scientists bring up more effective intervention and treatment strategies. New formulation approaches have been investigated to precisely deliver therapeutics to inflammatory lesions in the pancreas, and some even could directly attenuate the pancreatic damages. In this review, we will briefly introduce the involved pathogenesis and underlying mechanisms of acute pancreatitis, as well as the traditional Chinese medicine and the new drug option. Most of all, we will summarize the drug delivery strategies to reduce inflammation and potentially prevent the further development of pancreatitis, with an emphasis on the bifunctional nanoparticles that act as both drug delivery carriers and therapeutics.

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β‐Arrestin1 alleviates acute pancreatitis via repression of NF‐κBp65 activation

Abstract: β-Arr1 alleviates AP via repression of NF-κBp65 activation, and it is a potentially therapeutic target for AP.

Cited by 9 publications

References 37 publications

ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

Combinatory antibiotic treatment protects against experimental acute pancreatitis by suppressing gut bacterial translocation to pancreas and inhibiting NLRP3 inflammasome pathway

Drug discovery and formulation development for acute pancreatitis

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