Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis

Pereda, Javier; Sabater, Luís; Aparisi, Luís; Escobar, Javier; Sandoval, Juan; Viña, José; López-Rodas, Gerardo; Sastre, Juan

doi:10.2174/092986706778522011

Cited by 124 publications

(88 citation statements)

References 180 publications

(243 reference statements)

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“…First, pancreatic PTP1B deficient mice exhibited increased proinflammatory cytokines that play a significant role in the development and severity of the disease. 63 TNF-a exacerbates acinar cell injury, IL-1b regulates the development of AP, and IL-6 is a major mediator of the acute-phase response. Consistent with increased proinflammatory cytokines, knockout mice exhibited enhanced cerulein-and arginine-induced NF-kB signaling.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

Bettaieb

Koike

Chahed

et al. 2016

The American Journal of Pathology

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Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein-and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein-and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-a were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein-and arginine-induced NF-kB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein-and arginine-induced acute pancreatitis. (Am J Pathol 2016 http://dx

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Section: Discussionmentioning

confidence: 99%

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

Bettaieb

Koike

Chahed

et al. 2016

The American Journal of Pathology

Self Cite

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“…In scientific literature, there are many experimental evidences of a synergy between oxidative stress and proinflammatory cytokines in the development of the inflammatory response in AP (Denham et al, 1997;Pereda et al, 2004;Pereda et al, 2006). Moreover, pro-inflammatory cytokines and oxidative stress trigger common signal transduction pathways that lead to amplification of the inflammatory cascade (Shi et al, 2005;Pereda et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, increased oxidative stress appeared during pancreatitis in the course of AP (Dabrowski et al, 1999;Telek et al, 1999;Abu-Zidan et al, 2000;Shi et al, 2005). At present there are evidences of a synergy or the relationship between oxidative stress and pro-inflammatory cytokines in development of the inflammatory response in AP Pereda et al, 2006). In relation to this issue, Pereda et al have shown that simultaneous inhibition of TNF-α production and xanthine oxidase activity blocks to a great extent the local and systemic inflammatory response in AP .…”

Section: Introductionmentioning

confidence: 99%

“…The mortality due to AP is approximately 10%, but this estimate raise up to 20-30% in the severe forms of the disease due to multiple organ failure. Progress in medicine, mostly supportive and antibiotic therapy and surgery all has contributed to reduce mortality and morbidity rates in severe AP in the past decades (Pereda et al, 2006;Bang et al, 2008;Steer, 2008). However, no specific effective treatment has been reported in the clinical trials so far.…”

Section: Introductionmentioning

confidence: 99%

“…IL-l, IL-6 and TNF-α) (Reinheckel et al, 1998;Kyu et al, 2003;Pereda et al, 2006). Actived macrophages release pro-inflammatory cytokines in response to the local damage of the pancreas.…”

Section: Introductionmentioning

confidence: 99%

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The Combined Effects of Etanercept Plus Methylprednisolone on Pancreatic Oxidative Stress in Acute Pancreatitis Induced by Cerulein

Günay¹,

Kılıç²,

AMANVERMEZ³

2011

jecm

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KeywordsEtanercept Methylprednisolone Acute pancreatitis Oxidative stress Malondialdehyde Protein carbonyls ARTICLE INFO ABSTRACTWhether etanercept plus metylprednisolone reduce pancreatic oxidative stress and injury during pancreatitis is unknown well. The aim of this study was to examine the therapeutic effects of etanercept and methylprednisolone (MP) on acute pancreatitis and oxidative stress in acute pancreatitis (AP) induced by cerulein in a rat model. The study was performed with 48 rats divided into 6 groups (n = 8/group): 1-sham, 2-cerulein-induced pancreatitis (over 10 hours), 3-cerulein-pancreatitis (over 20 hours), 4-etanercept (5 mg/ kg, i.p.), 5-methylprednisolone (10 mg/kg, i.m.), 6-etanercept plus methylprednisolone. Also, the rats in groups 4, 5, and 6 were cerulein-induced pancreatitis at 20 hours. After the treatment, the pancreas and blood were taken for histopathological and biochemical analysis. All cerulein-treated rats developed biochemical and pathological acute pancreatitis after 10-20 hours. The markers of oxidative stress such as protein carbonyls, lipid peroxidation, and myeloperoxidase (mpo) in the pancreas tissues were increased in the group 2 and 3, but these were lower in etanercept and MP-treated rats compared to groups 3. Pancreatic mpo activity was considerably reduced in pancreas tissues at 20 h after the administration of etanercept plus metylprednisolone in the group 6 compared to group 3. In AP induced by cerulein, the treatment of etanercept plus methylprednisolone may ameliorate pancreatic oxidative stress in rats.

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Proteomic profiling in an animal model of acute pancreatitis

Fétaud¹,

Frossard

Farina³

et al. 2008

Proteomics

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Acute pancreatitis is an inflammatory disease of the pancreas, which evolves in approximately 20% of the patients to a severe illness associated with a high mortality rate. In this study, we performed a comparative proteomic analysis of pancreatic tissue extracts from rats with acute pancreatitis and healthy rodent controls in order to identify changes in protein expression related to the pathobiological processes of this disease. Pancreatic extracts from diseased and controls rats were analyzed by 2-DE and MS/MS. A total of 125 proteins were identified from both samples. Comparative analysis allowed the detection of 42 proteins or protein fragments differentially expressed between diseased and control pancreas, some of them being newly described in acute pancreatitis. Interestingly, these changes were representative of the main pathobiological pathways involved in this disease. We observed activation of digestive proteases and increased expression of various inflammatory markers, including several members of the alpha-macroglobulin family. We also detected changes related to oxidative and cell stress responses. Finally, we highlighted modifications of 14-3-3proteins that could be related to apoptosis regulation. These results showed the interest of proteomic analysis to identify changes characterizing pancreatic tissue damage and, therefore, to highlight new potential biomarkers of acute pancreatitis.

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Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis

Cited by 124 publications

References 180 publications

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

The Combined Effects of Etanercept Plus Methylprednisolone on Pancreatic Oxidative Stress in Acute Pancreatitis Induced by Cerulein

Proteomic profiling in an animal model of acute pancreatitis

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