Original ArticlePioglitazone, a PPAR-γ activator, attenuates the severity of cerulein-induced acute pancreatitis by modulating early growth response-1 transcription factor
Section snippets
Cell culture
The first set of experiments was designed to determine if PPAR-γ activators could inhibit the increased expression of Egr-1 observed in AR42J cells. Rat pancreatic acinar AR42J cells were obtained from the American Type Culture Collection and cultured in Dulbecco’s modified Eagle’s medium (DMEM, Sigma, St Louis, Mo) supplemented with 10% fetal bovine serum and antibiotics (100 U/mL penicillin and 100 mg/mL streptomycin) with 44 mM sodium bicarbonate and 10% CO2 as recommended.9 The acinar cells
Effects of PPAR-γ activators on Egr-1 expression and activity in cerulein-treated AR42J cells
Egr-1 mRNA levels measured by real-time RT- PCR 30 min after treatment with cerulein were markedly elevated in the group of cells treated with DMSO alone as a control (Fig 1, A and B). In cells treated with 20 μM or 40 μM pioglitazone, but otherwise subjected to identical cerulein procedures, Egr-1 mRNA levels were significantly reduced (P < 0.05).
Concordant with these observations, analyses of the expression of Egr-1 protein showed that pioglitazone significantly inhibited increased levels of
Discussion
Acute pancreatitis involves several separate processes, including acinar cell damage, thrombosis, increased vascular permeability, and local and systemic inflammation. These disease processes are initiated by pancreatic acinar cells in response to stress. To date, the mechanisms mediating these events are not well understood. Many acinar cell responses, especially the most rapid, include the activation of proteins by post-translational modifications, including stress kinases,12 trypsinogen,13
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