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

4 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

Cite this

Vosters, Olivier ; Beuneu, Claire ; Goldman, Michel ; Verhasselt, Valerie. / N-acetylcysteine derivative inhibits CD40-dependent proinflammatory properties of human pancreatic duct cells. In: Pancreas. 2008 ; Vol. 36, No. 4. pp. 363-368.
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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.",
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N-acetylcysteine derivative inhibits CD40-dependent proinflammatory properties of human pancreatic duct cells. / Vosters, Olivier; Beuneu, Claire; Goldman, Michel; Verhasselt, Valerie.

In: Pancreas, Vol. 36, No. 4, 05.2008, p. 363-368.

Research output: Contribution to journalArticle

TY - JOUR

T1 - N-acetylcysteine derivative inhibits CD40-dependent proinflammatory properties of human pancreatic duct cells

AU - Vosters, Olivier

AU - Beuneu, Claire

AU - Goldman, Michel

AU - Verhasselt, Valerie

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

KW - CD40

KW - pancreatic duct cells

KW - type 1 diabetes mellitus

KW - CAPAN-2

KW - NF-kappa B

KW - islet transplantation

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KW - AIRWAY EPITHELIAL-CELLS

KW - NECROSIS-FACTOR-ALPHA

KW - BETA-CELLS

KW - DENDRITIC CELLS

KW - CD40 LIGAND

KW - INFLAMMATORY MEDIATORS

KW - CYTOKINE PRODUCTION

KW - CROSS-LINKING

KW - ACINAR-CELLS

U2 - 10.1097/MPA.0b013e31815c75d4

DO - 10.1097/MPA.0b013e31815c75d4

M3 - Article

VL - 36

SP - 363

EP - 368

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 4

ER -