N-acetylcysteine derivative inhibits CD40-dependent proinflammatory properties of human pancreatic duct cells

Olivier Vosters, Claire Beuneu, Michel Goldman, Valerie Verhasselt

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objectives: We recently observed that duct cells constitutively express CD40, a membrane molecule whose engagement results in duct cell activation and proinflammatory cytokine secretion. This observation suggests a potential role of this pathway in the pathogenesis of type 1 diabetes, islet graft rejection, or acute pancreatitis. In this article, we investigated whether a salt derivative of N-acetyl-L-cysteine, Nacystelyn, could modulate CD40 expression on duct cells and the response of activated duct cells to CD40 engagement.

Methods: We assessed the effects of Nacystelyn on CD40 expression and function in human caucasian pancreatic adenocarcinoma, ATCC n-THB-80 (CAPAN-2) cells, a human pancreatic duct cell line. CD40 expression was analyzed by flow cytometry. To assess CAPAN-2 cell responses to CD40 engagement, we looked at nuclear factor-kappa B transcription factor activation using enzyme-linked immunosorbent assay and electrophoretic mobility shift assay and cytokine mRNA levels by quantitative real-time reverse transcriptase polymerase chain reaction.

Results: We observed that Nacystelyn dose-dependently inhibited CD40 expression on CAPAN-2 cells as well as CD40-induced nuclear factor kappa B activation and proinflammatory cytokines up-regulation.

Conclusions: Our data suggest that Nacystelyn could be considered as a useful tool to prevent immune and inflammatory responses in pancreatic disorders by interfering with the CD40 pathway in pancreatic duct cells.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalPancreas
Volume36
Issue number4
DOIs
Publication statusPublished - May 2008
Externally publishedYes

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