N-acetylcysteine derivative inhibits CD40-dependent proinflammatory properties of human pancreatic duct cells.
OBJECTIVE
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 degrees 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-kappaB 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 kappaB 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.
Vosters
Olivier
O
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium,
Beuneu
Claire
C
Goldman
Michel
M
Verhasselt
Valérie
V
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000473:pathology; D019013:CD40 Antigens / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics; D010183:Pancreatic Ducts / Q000187:drug effects / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects
D019013:CD40 Antigens; C086501:N-acetylcysteine lysinate; D016328:NF-kappa B; D008239:Lysine; D000111:Acetylcysteine