Nuclear factor kappa B–dependent gene transcription in cholecystokinin- and tumor necrosis factor-α–stimulated isolated acinar cells is regulated by p38 mitogen-activated protein kinase

Williard, Deborah E.; Twait, Erik; Yuan, Zhihang; Carter, A. Brent; Samuel, Isaac

doi:10.1016/j.amjsurg.2009.12.004

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…We have previously established our isolated acinar cell preparation and culture technique with good cell viability shown by adenosine triphosphate (ATP) assay and strong cell response to cholecystokinin stimulation measured by amylase release, while GFP expression visualized by fluorescent microscopy confirmed nearly 100% infection efficiency [28]. In the present study, we also prepared acinar cell smears for morphological analysis, at time zero and after 24 hrs in culture, using a cytocentrifuge (Shandon Inc., Pittsburgh, PA).…”

Section: Methodsmentioning

confidence: 86%

“…Lysates were prepared by homogenization of frozen portions of pancreas (or cell pellets) in HEPES lysis buffer [27], [28]. Samples with 40 µg total protein were denatured and subjected to SDS-PAGE on 12% gels, then transferred to PVDF membranes that were blotted against IL-33 rabbit polyclonal antibody (Santa Cruz Biotechnology, Santa Cruz, CA, Cat.…”

Section: Methodsmentioning

confidence: 99%

“…Pancreatic acinar cells were isolated from mice using a collagenase (Worthington Biochemical, Lake Wood, NJ) digestion procedure [28], [29]. Cells were maintained at 37°C in 95% air and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

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The Novel Cytokine Interleukin-33 Activates Acinar Cell Proinflammatory Pathways and Induces Acute Pancreatic Inflammation in Mice

et al. 2013

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BackgroundAcute pancreatitis is potentially fatal but treatment options are limited as disease pathogenesis is poorly understood. IL-33, a novel IL-1 cytokine family member, plays a role in various inflammatory conditions but its role in acute pancreatitis is not well understood. Specifically, whether pancreatic acinar cells produce IL-33 when stressed or respond to IL-33 stimulation, and whether IL-33 exacerbates acute pancreatic inflammation is unknown.Methods/ResultsIn duct ligation-induced acute pancreatitis in mice and rats, we found that (a) IL-33 concentration was increased in the pancreas; (b) mast cells, which secrete and also respond to IL-33, showed degranulation in the pancreas and lung; (c) plasma histamine and pancreatic substance P concentrations were increased; and (d) pancreatic and pulmonary proinflammatory cytokine concentrations were increased. In isolated mouse pancreatic acinar cells, TNF-α stimulation increased IL-33 release while IL-33 stimulation increased proinflammatory cytokine release, both involving the ERK MAP kinase pathway; the flavonoid luteolin inhibited IL-33-stimulated IL-6 and CCL2/MCP-1 release. In mice without duct ligation, exogenous IL-33 administration induced pancreatic inflammation without mast cell degranulation or jejunal inflammation; pancreatic changes included multifocal edema and perivascular infiltration by neutrophils and some macrophages. ERK MAP kinase (but not p38 or JNK) and NF-kB subunit p65 were activated in the pancreas of mice receiving exogenous IL-33, and acinar cells isolated from the pancreas of these mice showed increased spontaneous cytokine release (IL-6, CXCL2/MIP-2α). Also, IL-33 activated ERK in human pancreatic tissue.SignificanceAs exogenous IL-33 does not induce jejunal inflammation in the same mice in which it induces pancreatic inflammation, we have discovered a potential role for an IL-33/acinar cell axis in the recruitment of neutrophils and macrophages and the exacerbation of acute pancreatic inflammation.ConclusionIL-33 is induced in acute pancreatitis, activates acinar cell proinflammatory pathways and exacerbates acute pancreatic inflammation.

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Section: Methodsmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

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The Novel Cytokine Interleukin-33 Activates Acinar Cell Proinflammatory Pathways and Induces Acute Pancreatic Inflammation in Mice

et al. 2013

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“…Mechanisms other than Calcium or PKC dependent pathways have also been put forth, notable among these being angiotensin 2 acting through AT2 receptors (64) and p38/MAPK pathways (65, 66). In a recent study, the role of acinar cell injury by itself to activate inflammatory cascades was explored.…”

Section: Mechanisms Of Inflammatory Pathways Activationmentioning

confidence: 99%

Molecular mechanisms of pancreatic injury

Sah

Saluja

2011

Current Opinion in Gastroenterology

102

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Purpose of review The pathogenesis of acute pancreatitis (AP) is still not well understood. This articles reviews recent advances in our understanding of AP with emphasis on literature published during the last year. Recent Findings Zymogen activation was shown to be sufficient to induce AP. Another key early event, NFkB activation has previously been shown to induce AP. The relationship between these two key early steps is beginning to be clarified. The mechanisms responsible for zymogen activation- pathologic calcium signaling, pH changes, colocalization and autophagy; mechanisms of NFkB activation and potential therapeutic targets both upstream and downstream of these key events have been explored. Additional key findings have been elucidation of the dual role of oxidative stress in AP and role of bioenergetics in determining mode of cell death, recognition of endoplasmic reticulum stress as an early step and duct cells as important players in pancreatic injury. Summary Current findings have provided further insight into the roles and mechanisms of zymogen activation and inflammatory pathways in pancreatic injury. Future studies are being undertaken to establish the relative contributions of these pathways during acute pancreatitis which will be critical to identifying successful therapeutic targets.

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“…The activation of p38 in epithelial cells of exocrine tissues has been shown to modulate cell differentiation [11] and apoptosis [12], and mediate inflammatory responses [13]. To our knowledge, no previous studies of p38 function in the LG have been conducted other than for the use as a control for specificity of an inhibitor for another MAPK [14].…”

Section: Discussionmentioning

confidence: 99%

p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland

Carlsson

Gierow

2012

Cellular and Molecular Biology Letters

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Abstract:The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells.

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Nuclear factor kappa B–dependent gene transcription in cholecystokinin- and tumor necrosis factor-α–stimulated isolated acinar cells is regulated by p38 mitogen-activated protein kinase

Abstract: Background-Mitogen activated protein (MAP) kinases and nuclear factor kappa-B (NF-κB) are implicated in early stages of acute pancreatitis pathogenesis. We investigated the relationship between the p38 MAP kinase and NF-κB in isolated acinar cells.

Cited by 17 publications

References 36 publications

The Novel Cytokine Interleukin-33 Activates Acinar Cell Proinflammatory Pathways and Induces Acute Pancreatic Inflammation in Mice

The Novel Cytokine Interleukin-33 Activates Acinar Cell Proinflammatory Pathways and Induces Acute Pancreatic Inflammation in Mice

Molecular mechanisms of pancreatic injury

p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland

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