ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells.

摘要: The clinical course of chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) have an important role in the pathogenesis alcoholic CP. Chemokines recruit inflammatory cells, resulting inflammation. Although serum levels fractalkine (CX3CL1) are significantly elevated patients CP, mechanism this elevation remains unclear. This study aims to determine effects cytokines, pathogen-associated molecular patterns (PAMPs), ethanol its metabolites on CX3CL1 secretion by PSCs. Male Wistar/Bonn Kobori (WBN/Kob) rats aged 15 20 weeks were used as rodent models CP vivo. PSCs isolated from 6-week-old male Wistar rats. PAMPs, chemokine production activation signaling pathways vitro examined real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assay. Expression matrix metalloprotease (MMP)-2 was increased pancreas WBN/Kob rat expressed CX3CL1, MMP-2, a disintegrin domain (ADAM) 17. Cytokines PAMPs induced release activated extracellular signal-regulated kinase (ERK), MMP-9, ADAM17. suppressed specific inhibitors ERK, MMP, ADAM, ERK associated transcription. Ethanol phorbol myristate acetate synergistically release. Real-time PCR blotting confirmed synergistic via ADAM17 In conclusion, we demonstrated for first time that at least part through mitogen-activated protein might be one mechanisms disease progression