Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expressionin human pancreatic periacinar myofibroblasts

Background & Aims: We have previously isolated and characterized human panc reatic periacinar myofibroblasts, in this study, to define the role of thes e cells in the pathogenesis of acute pancreatitis, we investigated chemokin e expression in them. Methods: Secretion of chemokines (interlerkin [IL]-8, monocyte chemoattractant protein [MCP]-1, RANTES, and MIP [macrophage infl ammatory protein]-1 alpha) was evaluated by ELISA, Northern blotting, and n uclear run-on assays, The activation of NF-kappa B and NF-IL6 was assessed by an electrophoretic gel mobility shift assay. Results: IL-8 and MCP-1 sec retion was rapidly induced by both IL-1 beta and tumor necrosis factor (TNF )-alpha. RANTES secretion was induced more slowly and was induced mainly by TNF-alpha. However, MIP-1 alpha secretion was not induced by any stimuli. These responses were also observed at the messenger RNA level, and they wer e accompanied by an increase in transcriptional rate. The increase in trans criptional activation of chemokine genes correlated with the NF-kappa B and NF-IL6 activation. Furthermore, a blockade of NF-kappa B activation by PDT C and TPCK markedly reduced the IL-1 beta- or TNF-alpha-induced chemokine g ene expression. Conclusions: Chemokine secretion is differentially regulate d in pancreatic periacinar myofibroblasts, suggesting a role for these cell s in mediating the infiltration and accumulation of inflammatory cells in t he pancreas.