Obesity and Fat Distribution Imply a Greater Systemic Inflammatory Response and a Worse Prognosis in Acute Pancreatitis

“…These findings support the view that p38 MAP kinase regulates proinflammatory transcription factors such as NF-ĸB in pancreatic exocrine cells. This is significant because of the roles that CCK and TNF-α play in exacerbating acute inflammation in experimental models of acute pancreatitis [1,19,20,21,22,23]. Investigations using the donor rat model have shown that bile-pancreatic juice exclusion from gut exacerbates duct ligation-induced acute pancreatitis and also increases pancreatic phosphorylation of stress kinases (JNK, ERK, p38), activation of NF-ĸB, and production of proinflammatory mediators [15,24,25,26,27].…”

Section: Discussionmentioning

confidence: 99%

Dominant Negative p38 Mitogen-Activated Protein Kinase Expression Inhibits NF-κB Activation in AR42J Cells

2010

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Background: The role of the p38 mitogen-activated protein (MAP) kinase in acute pancreatitis pathogenesis is controversial. We hypothesize that p38 plays a role in regulating NF-ĸB activation in exocrine pancreatic cells. Methods: AR42J cells incorporating an NF-ĸB-responsive luciferase reporter, with and without adenoviral transduction of DNp38, were stimulated with cholecystokinin (CCK) or tumor necrosis factor-α (TNF-α) prior to measuring NF-ĸB activation. Results: CCK- or TNF-α-stimulated NF-ĸB-dependent gene transcription (luciferase assay) was substantially subdued by DNp38 expression. These findings were confirmed by electrophoretic mobility shift assay. Nuclear translocation of the p65 NF-ĸB subunit following agonist stimulation was evident (supershift). Characterization studies showed excellent adenoviral infection efficiency and cell viability in our AR42J cell model. Agonist-stimulated dose- and time-dependent p38 activation, with inhibition by DNp38 expression, was also confirmed. Conclusion: The p38 MAP kinase regulates NF-ĸB pathway activation in exocrine pancreatic cells, and thus potentially plays a role in the mechanism of acute pancreatitis pathogenesis.

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“…Despite an increasing knowledge of AP pathogenesis, there are still many questions concerning the role of WAT, obesity and adipohormones in this disease. On the other hand, in several studies obesity has been indentified as a risk factor for a poor outcome in AP [4,5]. …”

Section: Introductionmentioning

confidence: 99%

Circulating Levels of Visfatin, Resistin and Pro-Inflammatory Cytokine Interleukin-8 in Acute Pancreatitis

et al. 2010

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Obesity and Fat Distribution Imply a Greater Systemic Inflammatory Response and a Worse Prognosis in Acute Pancreatitis

Cited by 94 publications

References 42 publications

Overweight Is an Additional Prognostic Factor in Acute Pancreatitis: A Meta-Analysis

Overweight Is an Additional Prognostic Factor in Acute Pancreatitis: A Meta-Analysis

Dominant Negative p38 Mitogen-Activated Protein Kinase Expression Inhibits NF-κB Activation in AR42J Cells

Circulating Levels of Visfatin, Resistin and Pro-Inflammatory Cytokine Interleukin-8 in Acute Pancreatitis

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