Abstract
Aim: To test the hypothesis that cooperative interactions between transcription factors Nuclear Factor-kappa B (NF-κB) and Activator Protein-1 (AP1) augment transcriptional activity in exocrine pancreatic cells.
Highlights
Acute pancreatitis is common and is associated with substantial morbidity and mortality [1,2]
To determine the optimal stimulation time for Extracellular-Regulated Kinase (ERK) Mitogen-Activated Protein Kinases (MAPK) activation, AR42J cells were stimulated with TNF-α (100 ng/ml) or CCK8 (10 μM) for 1, 3, 5, 10 or 20 min prior to harvest
Immunoblots showed robust ERK MAPK phosphorylation (p-ERK) within 5 min of TNF-α stimulation, with a peak at 10 min, that returned to baseline levels by 20 min (Figure 2A)
Summary
Acute pancreatitis is common and is associated with substantial morbidity and mortality [1,2]. Cooperative interactions between NF-κB and AP-1 have the potential to amplify pro-inflammatory responses to exocrine pancreatic cell stress and exacerbate acute pancreatitis. NF-κB and AP-1 are ubiquitous transcription factors that regulate inflammatory and cell survival responses, are simultaneously activated by overlapping upstream kinases [e.g., Extracellular-Regulated Kinase (ERK)], and induce transcription of similar genes (Figure 1). Despite these close similarities, there are major differences in the regulation of NF-κB and AP-1 activation. IκB activation results in its own degradation with dissociation of the NF-κB/IκB complex, allowing nuclear translocation of NF-κB subunits and the ensuing gene transcription [3]. AP-1 is a dimeric transcription factor protein group (e.g., Jun, Fos) located in the nucleus [4,5,6]. c-Jun forms homodimers that bind DNA and has a key role in AP-1-dependent transcription as c-Fos depends upon heterodimerization with c-Jun to bind DNA, while c-Fos on its own does not bind to the AP-1 DNA site [7]
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