Deficiency of C/EBPβ in pancreatic acinar cells exacerbates inflammation in the early phase of acute pancreatitis.

Acute pancreatitis is a common gastrointestinal emergency with no specific therapeutic targets. CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates inflammatory gene expression through cooperation with NF-κB and STAT3 signaling pathways, but its role in acute pancreatitis remains unknown. Thus, we employed complementary experimental approaches to investigate C/EBPβ function in acute pancreatitis. In AR42J pancreatic acinar cells, C/EBPβ was knocked down by RNA interference followed by caerulein stimulation. In parallel, pancreas-specific C/EBPβ knockout mice (Cebpbflox/flox; Pdx1-Cre) were subjected to caerulein-induced acute pancreatitis model and evaluated by histological scoring, serum enzyme measurement, and RNA sequencing. Primary acinar cells isolated from knockout and control mice were also stimulated ex vivo. C/EBPβ expression was transiently induced in AR42J cells following caerulein stimulation. Knockdown of C/EBPβ significantly increased IL-6 mRNA expression after stimulation. Pancreas-specific C/EBPβ knockout mice exhibited significantly greater interstitial edema, leukocyte infiltration, and subsequent acinar cell necrosis compared with control mice. Gene set enrichment analysis revealed upregulated activation of IL-6/JAK/STAT3 signaling pathways in knockout mice. Furthermore, primary acinar cells from knockout mice showed significantly elevated Il6 expression upon caerulein stimulation. C/EBPβ plays a protective role in the early phase of acute pancreatitis by suppressing IL-6-driven inflammatory responses in pancreatic acinar cells, identifying C/EBPβ as a potential regulatory factor in acute pancreatitis pathogenesis.