Introduction: Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis.

Aims: To examine the role of PSCs in pancreatic inflammation by determining whether activated PSCs express intercellular adhesion molecule-1 (ICAM-1).

Methodology: Culture-activated rat PSCs were treated with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), ethanol, or acetaldehyde. ICAM-1 expression was analyzed by flow cytometry. The induction of mRNA was assessed by Northern blot analysis. The binding activity of transcription factors was examined by electrophoretic mobility shift assay. The activation of mitogen-activated protein kinases was assessed by Western blotting with use of antiphosphospecific antibodies. The adhesion of MOLT-4 cells to activated PSCs was also assessed.

Results: Culture-activated PSCs expressed ICAM-1. The expression was increased in response to IL-1 beta and TNF-alpha but not to alcohol, with comparable mRNA induction. IL-1 beta and TNF-alpha increased the nuclear factor-kappa B (NF-kappa B)-specific and activator protein-1-specific DNA binding activity, whereas the NF-IL6 activity was not altered. Alcohol did not increase NF-kappa B binding activity. IL-1 beta and TNF-alpha activated extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinase. Inducible ICAM-1 expression was blocked by pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappa B activation, but not by inhibitors of mitogen-activated protein kinase pathways. IL-1 beta and TNF-alpha increased the ICAM-1-mediated binding of MOLT-4 cells to activated PSCs, indicating a role of ICAM-1 in the adhesion of leukocytes to PSCs.

Conclusion: Our results suggest that activated PSCs express ICAM-1 mainly through the activation of NF-kappa B, thus playing a role in the pathogenesis of pancreatic inflammation.

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Source
http://dx.doi.org/10.1097/00006676-200207000-00018DOI Listing

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