scholarly journals Inflammatory Response on the Pancreatic Acinar Cell Injury

2005 ◽  
Vol 94 (2) ◽  
pp. 97-102 ◽  
Author(s):  
M. Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Acinar Cell ◽  
Cell Injury ◽  
Critical Role ◽  
Organ Damage ◽  
Multiple Organ ◽  
Pancreatic Acinar Cell ◽  
Inflammatory Disorder ◽  
Distant Organ

Acute pancreatitis is an inflammatory disorder, and inflammation not only affects the pathogenesis but also the course of the disease. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-α, IL-1β, IL-6, IL-8, CINC/GRO-α, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, MIP1-α, RANTES, substance P, and hydrogen sulfide in acute pancreatitis and the resultant MODS. This review intends to present an overview of the inflammatory response that takes place following pancreatic acinar cell injury.

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL)

2009 ◽  
Vol 297 (6) ◽  
pp. G1163-G1171 ◽  
Author(s):  
Marco Siech ◽  
Zhengfei Zhou ◽  
Shaoxia Zhou ◽  
Bernd Bair ◽  
Andreas Alt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Acinar Cell ◽  
Cell Injury ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Stellate Cells ◽  
Matrix Synthesis ◽  
Repair Mechanisms

Mechanisms leading to acute pancreatitis after a fat-enriched meal combined with excess alcohol are incompletely understood. We have studied the effects of alcohol and fat (VLDL) on pancreatic acinar cell (PAC) function, oxidative stress, and repair mechanisms by pancreatic stellate cells (PSC) leading to fibrogenesis. To do so, PAC (rat) were isolated and cultured up to 24 h. Ethanol and/or VLDL were added to PAC. We measured PAC function (amylase, lipase), injury (lactic dehydrogenase), apoptosis (TUNEL, Apo2.7, annexin V binding), oxidative stress, and lipid peroxidation (conjugated dienes, malondialdehyde, chemoluminescence); we also measured PSC proliferation (bromodeoxyuridine incorporation), matrix synthesis (immunofluorescence of collagens and fibronectin, fibronectin immunoassay), and fatty acids in PAC supernatants (gas chromatography). Within 6 h, cultured PAC degraded and hydrolyzed VLDL completely. VLDL alone (50 μg/ml) and in combination with alcohol (0.2, 0.5, and 1% vol/vol) induced PAC injury (LDL, amylase, and lipase release) within 2 h through generation of oxidative stress. Depending on the dose of VLDL and alcohol, apoptosis and/or necrosis were induced. Antioxidants (Trolox, Probucol) reduced the cytotoxic effect of alcohol and VLDL. Supernatants of alcohol/VLDL-treated PAC stimulated stellate cell proliferation and extracellular matrix synthesis. We concluded that, in the presence of lipoproteins, alcohol induces acinar cell injury. Our results provide a biochemical pathway for the clinical observation that a fat-enriched meal combined with excess alcohol consumption can induce acinar cell injury (acute pancreatitis) followed by repair mechanisms (proliferation and increased matrix synthesis in PSC).

Substance P treatment stimulates chemokine synthesis in pancreatic acinar cells via the activation of NF-κB

2006 ◽  
Vol 291 (6) ◽  
pp. G1113-G1119 ◽  
Author(s):  
Raina Devi Ramnath ◽  
Madhav Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Substance P ◽  
Acinar Cell ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Chemokine Production ◽  
Pancreatic Acini ◽  
Monocyte Chemoattractant Protein 1

Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction and to the subsequent systemic inflammatory response, which may result in multiple organ dysfunction and death. Inflammatory mediators, including chemokines and substance P (SP), are known to play a crucial role in the pathogenesis of acute pancreatitis. It has been shown that pancreatic acinar cells produce the chemokine monocyte chemoattractant protein-1 (MCP-1) in response to caerulein hyperstimulation, demonstrating that acinar-derived MCP-1 is an early mediator of inflammation in acute pancreatitis. Similarly, SP levels in the pancreas and pancreatic acinar cell expression of neurokinin-1 receptor, the primary receptor for SP, are both increased during secretagogue-induced experimental pancreatitis. This study aims to examine the functional consequences of exposing mouse pancreatic acinar cells to SP and to determine whether it leads to proinflammatory signaling, such as production of chemokines. Exposure of mouse pancreatic acini to SP significantly increased synthesis of MCP-1, macrophage inflammatory protein-1α (MIP-1α), as well as MIP-2. Furthermore, SP also increased NF-κB activation. The stimulatory effect of SP was specific to chemokine synthesis through the NF-κB pathway, since the increase in chemokine production was completely attenuated when pancreatic acini were pretreated with the selective NF-κB inhibitor NF-κB essential modulator-binding domain peptide. This study shows that SP-induced chemokine synthesis in mouse pancreatic acinar cells is NF-κB dependent.

Cathepsin B inhibition prevents trypsinogen activation and reduces pancreatitis severity

2002 ◽  
Vol 283 (3) ◽  
pp. G794-G800 ◽  
Author(s):  
Gijs J. D. van Acker ◽  
Ashok K. Saluja ◽  
Lakshmi Bhagat ◽  
Vijay P. Singh ◽  
Albert M. Song ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cell ◽  
Cathepsin B ◽  
Cell Activation ◽  
Cell Injury ◽  
Critical Role ◽  
Trypsinogen Activation ◽  
Soluble Cell

Intrapancreatic activation of trypsinogen is believed to play a critical role in the initiation of acute pancreatitis, but mechanisms responsible for intrapancreatic trypsinogen activation during pancreatitis have not been clearly defined. In previous in vitro studies, we have shown that intra-acinar cell activation of trypsinogen and acinar cell injury in response to supramaximal secretagogue stimulation could be prevented by the cell permeant cathepsin B inhibitor E64d (Saluja A, Donovan EA, Yamanaka K, Yamaguchi Y, Hofbauer B, and Steer ML. Gastroenterology 113: 304–310, 1997). The present studies evaluated the role of intrapancreatic trypsinogen activation, this time under in vivo conditions, in two models of pancreatitis by using another highly soluble cell permeant cathepsin B inhibitor,l-3-trans-(propylcarbamoyl)oxirane-2-carbonyl-l-isoleucyl-l-proline methyl ester (CA-074me). Intravenous administration of CA-074me (10 mg/kg) before induction of either secretagogue-elicited pancreatitis in mice or duct infusion-elicited pancreatitis in rats markedly reduced the extent of intrapancreatic trypsinogen activation and substantially reduced the severity of both pancreatitis models. These observations support the hypothesis that, during the early stages of pancreatitis, trypsinogen activation in the pancreas is mediated by the lysosomal enzyme cathepsin B. Our findings also suggest that pharmacological interventions that inhibit cathepsin B may prove useful in preventing acute pancreatitis or reducing its severity.

Mechanisms of Acinar Cell Injury in Acute Pancreatitis

2005 ◽  
Vol 94 (2) ◽  
pp. 89-96 ◽  
Author(s):  
M. G. T. Raraty ◽  
J. A. Murphy ◽  
E. McLoughlin ◽  
D. Smith ◽  
D. Criddle ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cell ◽  
Cell Injury ◽  
Research Effort ◽  
Cytosolic Calcium ◽  
Pancreatic Acinar Cell ◽  
Enzyme Activation ◽  
Cellular Damage ◽  
Extracellular Milieu ◽  
The Subject

Acute pancreatitis has many causes, all leading to a common pathway of changes within the pancreatic acinar cell. Key amongst these changes is premature intracellular activation of digestive enzymes but this is also accompanied by the appearance of cytosolic vacuoles, co-localization of digestive and lysosomal enzymes, activation of NF-kB, and release of pro-inflammatory cytokines. The exact mechanism responsible for enzyme activation remains the subject of much research effort and not a little debate, however it is clear that all of these changes are triggered by an abnormal, sustained rise in cytosolic calcium concentration, which is itself dependent both on release of calcium from endoplasmic reticulum stores and uptake from the extracellular milieu. Activated enzymes are directly damaging to the acinar cell themselves, but recruitment of circulating neutrophils leads to further cellular damage. Cytokines and neutrophil activation are also responsible for the systemic inflammatory response typically seen in severe acute pancreatitis.

Apoptosis versus necrosis in acute pancreatitis

2004 ◽  
Vol 286 (2) ◽  
pp. G189-G196 ◽  
Author(s):  
Madhav Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Cell Death ◽  
Acinar Cell ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Experimental Studies ◽  
Acinar Cells ◽  
Inflammatory Cells ◽  
Pancreatic Acinar Cell ◽  
Mild Acute Pancreatitis

Acute pancreatitis is a disease of variable severity in which some patients experience mild, self-limited attacks, whereas others manifest a severe, highly morbid, and frequently lethal attack. The events that regulate the severity of acute pancreatitis are, for the most part, unknown. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells and result in acinar cell injury. Other processes, such as recruitment of inflammatory cells and generation of inflammatory mediators, are believed to occur subsequent to acinar cell injury, and these “downstream” events are believed to influence the severity of the disease. Several recently reported studies, however, have suggested that the acinar cell response to injury may, itself, be an important determinant of disease severity. In these studies, mild acute pancreatitis was found to be associated with extensive apoptotic acinar cell death, whereas severe acute pancreatitis was found to involve extensive acinar cell necrosis but very little acinar cell apoptosis. These observations led to the hypothesis that apoptosis could be a favorable response to acinar cells and that interventions that favor induction of apoptotic, as opposed to necrotic, acinar cell death might reduce the severity of an attack of acute pancreatitis. Indeed, in an experimental setting, the induction of pancreatic acinar cell apoptosis protects mice against acute pancreatitis. Little is known about the mechanism of apoptosis in the pancreatic acinar cell, although some early attempts have been made in that direction. Also, clinical relevance of these experimental studies remains to be investigated.

Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration

2003 ◽  
Vol 38 (3) ◽  
pp. 260-267 ◽  
Author(s):  
Tsunao Imamura ◽  
Junichi Niikawa ◽  
Katsuya Kitamura ◽  
Akira Takahashi ◽  
Akitoshi Ikegami ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cell ◽  
Pancreatic Acinar Cell ◽  
Cell Regeneration

scholarly journals Systemic inflammatory response syndrome and multiple-organ damage / dysfunction in complicated canine babesiosis

2001 ◽  
Vol 72 (3) ◽  
Author(s):  
C. Welzl ◽  
A.L. Leisewitz ◽  
L.S. Jacobson ◽  
T. Vaughan-Scott ◽  
E. Myburgh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Renal Involvement ◽  
Organ Damage ◽  
Multiple Organ ◽  
Systemic Inflammatory Response ◽  
The Body ◽  
Increased Risk

This study was designed to document the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retro-spectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are manysimilarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.

Decreased S1P and SPHK2 are involved in pancreatic acinar cell injury

2019 ◽  
Vol 13 (8) ◽  
pp. 627-637 ◽  
Author(s):  
Juan Xiao ◽  
Houmin Lin ◽  
Binggang Liu ◽  
Zhijia Xia ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Injury ◽  
Pancreatic Acinar Cell

scholarly journals Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xian-lin Wu ◽  
Jie-xing Li ◽  
Zhen-dong Li ◽  
Da-sheng Liu ◽  
Su-hong Lu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Free Radical ◽  
Bile Duct ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Protective Effect ◽  
Severe Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction

Tet is a type of alkaloid extracted fromStephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

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