scholarly journals TRANSGENIC EXPRESSION OF THE NF??B SUBUNIT p65 IN PANCREATIC ACINAR CELLS OF TRANSGENIC MICE INCREASES THE SEVERITY OF ACUTE PANCREATITIS

Pancreas ◽  
2005 ◽  
Vol 31 (4) ◽  
pp. 448
Author(s):  
Baoan Ji ◽  
Jian Song ◽  
Craig D Logsdon
Keyword(s):  
Acute Pancreatitis ◽  
Transgenic Mice ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Transgenic Expression ◽  
B Subunit

scholarly journals Transgenic expression of cyclooxygenase-2 in pancreatic acinar cells induces chronic pancreatitis

2019 ◽  
Vol 316 (1) ◽  
pp. G179-G186
Author(s):  
Haojie Huang ◽  
Jiaxiang Chen ◽  
Lisi Peng ◽  
Yao Yao ◽  
Defeng Deng ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Transgenic Mice ◽  
Fibrous Tissue ◽  
Acinar Cells ◽  
Cyclooxygenase 2 ◽  
Therapeutic Interventions ◽  
Pancreatic Stellate Cells ◽  
Pancreatic Acinar Cells ◽  
Transgenic Expression ◽  
Cox 2

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. However, it is unknown whether COX-2 can cause chronic pancreatitis. To investigate the roles of pancreatic acinar COX-2 in fibrogenesis and the development of chronic pancreatitis, COX-2 was ectopically expressed specifically in pancreatic acinar cells in transgenic mice. Histopathological changes and expression levels of several profibrogenic factors related to chronic pancreatitis were evaluated. COX-2 was expressed in the pancreas of the transgenic mice, as detected by Western blot analysis. Immunohistochemical staining showed COX-2 was specifically expressed in pancreatic acinar cells. COX-2 expression led to progressive changes in the pancreas, including pancreas megaly, persistent inflammation, collagen deposition, and acinar-to-ductal metaplasia. Quantitative RT-PCR and immunostaining showed that profibrogenic factors were upregulated and pancreatic stellate cells were activated in the COX-2 transgenic mice. Expression of COX-2 in pancreatic acinar cells is sufficient to induce chronic pancreatitis. Targeting this pathway may be valuable in the prevention of chronic pancreatitis. NEW & NOTEWORTHY COX-2 expression is observed in pancreatic tissues of human chronic pancreatitis. In this study, we showed that COX-2 expression caused the development of chronic pancreatitis in transgenic mice, supporting the idea that COX-2 inhibition may be an effective preventive and therapeutic strategy.

scholarly journals Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms

2014 ◽  
Vol 307 (9) ◽  
pp. G941-G949 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Rubina Kapadia ◽  
Arundhati Biswas ◽  
Hamid M. Said
Keyword(s):  
Transgenic Mice ◽  
Chronic Exposure ◽  
Methylation Status ◽  
Acinar Cells ◽  
Alcohol Exposure ◽  
Significant Inhibition ◽  
Pancreatic Acinar Cells ◽  
Chronic Alcohol ◽  
Wild Type ◽  
Chronic Alcohol Exposure

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

scholarly journals Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ali A. Aghdassi ◽  
Daniel S. John ◽  
Matthias Sendler ◽  
Christian Storck ◽  
Cindy van den Brandt ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Serine Protease ◽  
Acinar Cells ◽  
Neutrophil Infiltration ◽  
Cathepsin G ◽  
Pancreatic Acinar Cells ◽  
Neutrophil Granulocyte ◽  
Zymogen Activation ◽  
Trypsinogen Activation ◽  
Extracellular Matrix Components

AbstractAcute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG−/− mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG−/− mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected.

TRANSCRIPTION FACTOR PROFILING OF PANCREATIC ACINAR CELLS FOLLOWING TNF-α INDUCTION OF ACUTE PANCREATITIS.

Shock ◽  
2003 ◽  
Vol 19 (Supplement) ◽  
pp. 20
Author(s):  
L. Vona-Davis ◽  
K. Magabo ◽  
B. Jackson ◽  
T. Evans ◽  
D. Riggs ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Transcription Factor ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Tnf Α

Acinar Akt1 in pancreatic acinar cells supports proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S101
Author(s):  
Rong Chen ◽  
Ermanno Malagola ◽  
Maren Dietrich ◽  
Richard Zuellig ◽  
Marta Bombardo ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Acinar To Ductal Metaplasia

scholarly journals Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models

2015 ◽  
Vol 149 (2) ◽  
pp. 481-492.e7 ◽  
Author(s):  
Li Wen ◽  
Svetlana Voronina ◽  
Muhammad A. Javed ◽  
Muhammad Awais ◽  
Peter Szatmary ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Mouse Models ◽  
Acinar Cells ◽  
Cytosolic Calcium ◽  
Pancreatic Acinar Cells ◽  
Associated Injury

Metallothionein is a component of exocrine pancreas secretion: implications for zinc homeostasis

1996 ◽  
Vol 271 (4) ◽  
pp. C1103-C1110 ◽  
Author(s):  
R. C. De Lisle ◽  
M. P. Sarras ◽  
J. Hidalgo ◽  
G. K. Andrews
Keyword(s):  
Transgenic Mice ◽  
Pancreatic Juice ◽  
Secretory Pathway ◽  
Physiological Role ◽  
Acinar Cells ◽  
Transgenic Animals ◽  
Light Level ◽  
Zinc Homeostasis ◽  
Pancreatic Acinar Cells ◽  
Pancreatic Ducts

Using transgenic mice that overexpress metallothionein-I (MT-I) and zinc-induced normal and transgenic animals, we have explored the localization of MT in the pancreas. Light-level immunocytochemistry demonstrated MT in acinar cells but not islet cells. Immunolabeling also revealed the presence of MT in pancreatic ducts, suggesting that it is released from acinar cells. Ultrastructural immunolocalization showed that MT was cytoplasmic, and no MT immunoreactivity was detected in lumens of the vesicular secretory pathway. Secreted pancreatic juice was collected from pilocarpine-stimulated mice and assayed for MT by a 109Cd-labeled hemoglobin-exchange assay and by radioimmunoassay. Both methods revealed high (> 1,000 ng/ml) levels of MT in the stimulated secretion. The level of MT in pancreatic juice from transgenic mice was only slightly (2-fold) increased despite dramatic overexpression of MT-I in the pancreas (> 20-fold). In contrast, zinc induction of MT significantly increased MT by 5- to 10-fold in the pancreatic juice, in normal and transgenic mice. These data indicate that MT is released from pancreatic acinar cells but not by the classical vesicular secretory pathway. In addition, MT levels in pancreatic juice are regulated by zinc, suggesting a physiological role of the pancreas in metal homeostasis.

scholarly journals CaMKII/proteasome/cytosolic calcium/cathepsin B axis was present in tryspin activation induced by nicardipine

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Juan Xiao ◽  
Houmin Lin ◽  
Binggang Liu ◽  
Junfei Jin
Keyword(s):  
Acute Pancreatitis ◽  
Calcium Channel ◽  
Cathepsin B ◽  
Acinar Cells ◽  
Proteasome Inhibition ◽  
Cytosolic Calcium ◽  
Pancreatic Acinar Cells ◽  
Prolonged Treatment ◽  
Early Event ◽  
Trypsinogen Activation

Abstract Premature trypsinogen activation is the early event of acute pancreatitis. Therefore, the studies on the processes of trypsinogen activation induced by compounds are important to understand mechanism underly acute pancreatitis under various conditions. Calcium overload in the early stage of acute pancreatitis was previously found to cause intracellular trypsinogen activation; however, treatment of acute pancreatitis using calcium channel blockers did not produced consistent results. Proteasome activity that could be inhibited by some calcium channel blocker has recently been reported to affect the development of acute pancreatitis; however, the associated mechanism were not fully understood. Here, the roles of nicardipine were investigated in trypsinogen activation in pancreatic acinar cells. The results showed that nicardipine could increase cathepsin B activity that caused trypsinogen activation, but higher concentration of nicardipine or prolonged treatment had an opposite effect. The effects of short time treatment of nicardipine at low concentration were studied here. Proteasome inhibition was observed under nicardipine treatment that contributed to the up-regulation in cytosolic calcium. Increased cytosolic calcium from ER induced by nicardipine resulted in the release and activation of cathepsin B. Meanwhile, calcium chelator inhibited cathepsin B as well as trypsinogen activation. Consistently, proteasome activator protected acinar cells from injury induced by nicardipine. Moreover, proteasome inhibition caused by nicardipine depended on CaMKII. In conclusion, CaMKII down-regulation/proteasome inhibition/cytosolic calcium up-regulation/cathepsin B activation/trypsinogen activation axis was present in pancreatic acinar cells injury under nicardipine treatment.

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