Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

Wei, Sha Xin; Huang, Qingyong; Li, Jinzheng; Liu, Zuojin; You, Hai-bo; Yong, Chen; Gong, Jianping

doi:10.1007/s10753-011-9362-0

Cited by 27 publications

(16 citation statements)

References 44 publications

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“…Moreover, pretreatment with taurine significantly reduced the levels of TNF and IL1β in a rat model of severe acute pancreatitis. In this model, taurine also inhibited MAPK14 expression and its activation through phosphorylation (17). …”

Section: Osmolytes and Inflammationmentioning

confidence: 95%

“…Osmolyte accumulation within the cell equalizes intracellular osmotic pressure with that of the extracellular environment. It is also interesting to note that experiments have shown supplementation with a variety of osmolytes reduces inflammatory cytokine release and inflammation (12–17). Intracellular accumulation of these compounds has little effect on cellular homeostasis because most are neutral at physiological pH, i.e., either lack charge or are zwitterionic.…”

Section: Osmolytes and Inflammationmentioning

confidence: 99%

“…Only a small increase in extracellular osmolarity above the physiological range is necessary to elicit cytokine secretion (11). Studies have also shown that many osmolytes synthesized in response to osmotic stress can reduce inflammation (12–17). A number of disorders are associated with local and systemic elevations in extracellular fluid osmolarity, including diabetes, inflammatory bowel disease, hypernatremia, and dry eye syndrome, to name a few (11, 18–20).…”

Section: Introductionmentioning

confidence: 99%

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The role of hyperosmotic stress in inflammation and disease

Brocker

Thompson²,

Vasiliou

2012

BioMolecular Concepts

229

212

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Hyperosmotic stress is an often overlooked process that potentially contributes to a number of human diseases. Whereas renal hyperosmolarity is a well-studied phenomenon, recent research provides evidence that many non-renal tissues routinely experience hyperosmotic stress that may contribute significantly to disease initiation and progression. Moreover, a growing body of evidence implicates hyperosmotic stress as a potent inflammatory stimulus by triggering proinflammatory cytokine release and inflammation. Under physiological conditions, the urine concentrating mechanism within the inner medullary region of the mammalian kidney exposes cells to high extracellular osmolarity. As such, renal cells have developed many adaptive strategies to compensate for increased osmolarity. Hyperosmotic stress is linked to many maladies, including acute and chronic, as well as local and systemic, inflammatory disorders. Hyperosmolarity triggers cell shrinkage, oxidative stress, protein carbonylation, mitochondrial depolarization, DNA damage, and cell cycle arrest, thus rendering cells susceptible to apoptosis. However, many adaptive mechanisms exist to counter the deleterious effects of hyperosmotic stress, including cytoskeletal rearrangement and up-regulation of antioxidant enzymes, transporters, and heat shock proteins. Osmolyte synthesis is also up-regulated and many of these compounds have been shown to reduce inflammation. The cytoprotective mechanisms and associated regulatory pathways that accompany the renal response to hyperosmolarity are found in many non-renal tissues, suggesting cells are commonly confronted with hyperosmotic conditions. Osmoadaptation allows cells to survive and function under potentially cytotoxic conditions. This review covers the pathological consequences of hyperosmotic stress in relation to disease and emphasizes the importance of considering hyperosmolarity in inflammation and disease progression.

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Section: Osmolytes and Inflammationmentioning

confidence: 95%

Section: Osmolytes and Inflammationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of hyperosmotic stress in inflammation and disease

Brocker

Thompson²,

Vasiliou

2012

BioMolecular Concepts

229

212

View full text Add to dashboard Cite

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“…Nuclear factor kB (NFkB) and p38 are involved in several inflammatory cytokine responses such as the pathways that mediate endotoxins that cause liver damage (Kolios et al, 2006;Luckey & Petersen, 2001). Blocking the NFkB or p38 signaling pathways inhibits a positive feedback loop that is mediated by proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-a that attenuate inflammation (Wei et al, 2012;Yang et al, 2005). Crude extracts of S. miltiorrhiza enhance phagocytosis by KCs, reduce endotoxin secretion, and inhibit cytokine secretion during endotoxemia (Liang et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Salvia miltiorrhizacompounds protect the liver from acute injury by regulation of p38 and NFκB signaling in Kupffer cells

Yue

Wang

et al. 2014

Pharmaceutical Biology

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Context: Salvia miltiorrhiza Bunge is a traditional Asian medicine used to treat cerebral and cardiac ischemia. However, the effects of the active compounds of S. miltiorrhiza on liver damage are unclear. Objective: In this study, we tested the effects on acute liver injury of crude S. miltiorrhiza extracts from roots as well as neotanshinone B, dehydromiltirone, tanshinol A, tanshinone I, dihydrotanshinono I, neotanshinone A, cryptanshinono, tanshinone II A, and salvianolie acid B from purified S. miltiorrhiza extracts. Materials and methods: Various compounds or ethanol extract of S. miltiorrhiza (50, 100, and 200 mg/kg, p.o.) were administered to rats for five consecutive days. After acute carbon tetrachloride (CCl 4 )-induced liver injury by treatment of rats with a single dose of CCl 4 (0.75 mL/kg, p.o), rat liver function was tested by measuring serum biochemical parameters. Serum cytokine concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). Expression of p38 and NFkB was evaluated by western blot. Results: All S. miltiorrhiza components showed their effects on liver function from the dose from 50 to 200 mg/kg. At the dose of 200 mg/kg, they reduced serum levels of alkaline phosphatase (ALP) by 34-77%, alanine aminotransferase (ALT) by 30-57%, aspartate aminotransferase (AST) by 43-72%, creatine total bilirubin (BIL-T) by 33-81%, albumin (ALB) by 37-67%, indicating that S. miltiorrhiza extracts protected liver from CCl 4 -induced damage. Moreover, S. miltiorrhiza extracts at 200 mg/kg reduced the increase in the proinflammatory cytokines tumor necrosis factor-a (TNF-a) by 25-82%, interleukin-1 (IL-1) by 42-74% and interleukin-6 (IL-6) by 67-83%, indicating an effect on alleviating liver inflammation. Furthermore, in vitro, S. miltiorrhiza extracts inhibited p38 and NFkB signaling in Kupffer cells. This effect could be a main mechanism by which S. miltiorrhiza protects against acute liver toxicity. Discussion and conclusion: Active compounds of S. miltiorrhiza protected the liver from CCl 4 -induced injury. Protection might have been due to inhibition of p38 and NFkB signaling in Kupffer cells, which subsequently reduced inflammation in the liver.

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“…Liver macrophages usually contribute to the occurrence and amplification of systemic inflammation after the development of acute pancreatitis [17]; [18]. However, there are few studies that confirm which polarization of liver macrophages occurs in the process of acute pancreatitis and its relationship with the severity of this disease.…”

Section: Introductionmentioning

confidence: 99%

Induction of M2 Polarization in Primary Culture Liver Macrophages from Rats with Acute Pancreatitis

Yang

Lin

et al. 2014

PLoS ONE

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Background and AimsSystemic inflammatory response syndrome (SIRS), a major process of severe acute pancreatitis (SAP), usually occurs after various activated proinflammatory cytokines, which are produced by macrophages such as liver macrophages. Macrophages can secrete not only proinflammatory mediators but also inhibitory inflammatory cytokines such as IL-10, leading to two different functional states defined as “polarization”. The main purpose of this study was to demonstrate the polarization of liver macrophages during severe acute pancreatitis and to explore whether the polarization of these activated Liver macrophages could be reversed in vitro.MethodsLiver macrophages were isolated from rats with acute pancreatitis. These primary culture macrophages were treated with IL-4 or regulatory T cells in vitro to reverse their polarization and was evaluated by measuring M1/M2 marker expression using real time PCR and immunofluorescence staining.ResultsAcute pancreatitis was induced successfully by intra-pancreatic ductal injection of 5% sodium taurocholate. The liver macrophages demonstrated M1 polarization from 4 h to 16 h after the onset of acute pancreatitis. However, after IL-4 or Treg treatment, the polarization of the liver macrophages was reversed as indicated by increased expression of M2 markers and reduced expression of M1 markers. Furthermore, the effect of Treg on modulating macrophage polarization was slightly better than that of IL-4 in vitro.ConclusionLiver macrophages, a pivotal cell type in the pathogenesis of SAP, become M1 polarized during pancreatic inflammation. Treatment of these cells with IL-4 and Treg can reverse this activation in vitro. This method of altering macrophage polarization could be a prospective therapy for SAP.

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Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

Cited by 27 publications

References 44 publications

The role of hyperosmotic stress in inflammation and disease

The role of hyperosmotic stress in inflammation and disease

Salvia miltiorrhizacompounds protect the liver from acute injury by regulation of p38 and NFκB signaling in Kupffer cells

Induction of M2 Polarization in Primary Culture Liver Macrophages from Rats with Acute Pancreatitis

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