Pyrrolidinedithiocarbamate inhibits NF-κB activation and IL-8 production in intestinal epithelial cells

Zoltán H. Németh, Edwin A. Deitch, Csaba Szabo, György Haskó

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

During inflammatory bowel disease and intestinal ischemia, epithelial cells of the gut mucosa produce various inflammatory mediators, including the chemokine interleukin (IL-8). This IL-8 produced by intestinal epithelial cells has recently been implicated as a contributory factor to the deleterious inflammatory process resulting in colitis during inflammatory bowel disease or multiple organ failure following shock and trauma. Recent evidence suggests that the transcription factor nuclear factor κB (NF-κB) is a central regulator of IL-8 gene expression. In the present paper we investigated the effect of pharmacological inhibition of NF-κB with pyrrolidinedithiocarbamate (PDTC) on IL-1β-induced IL-8 production by the human intestinal epithelial cell line HT-29. Pretreatment of cells with PDTC (3-1000 μM) dose-dependently attenuated IL-8 production. Furthermore, PDTC (100 μM) suppressed the accumulation of IL-8 mRNA. PDTC inhibited the activation of NF-κB, because PDTC suppressed both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Taken together, our data demonstrate that NF-κB inhibition with PDTC decreases IL-8 production by intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalImmunology Letters
Volume85
Issue number1
DOIs
StatePublished - Jan 2 2003
Externally publishedYes

Fingerprint

Interleukin-8
Epithelial Cells
Inflammatory Bowel Diseases
Multiple Organ Failure
pyrrolidine dithiocarbamic acid
Colitis
Interleukin-1
Chemokines
Shock
Mucous Membrane
Transcription Factors
Ischemia
Pharmacology
Gene Expression
Cell Line
Messenger RNA
DNA
Wounds and Injuries

Keywords

  • Crohn's disease
  • Sepsis
  • Transcription factor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Pyrrolidinedithiocarbamate inhibits NF-κB activation and IL-8 production in intestinal epithelial cells. / Németh, Zoltán H.; Deitch, Edwin A.; Szabo, Csaba; Haskó, György.

In: Immunology Letters, Vol. 85, No. 1, 02.01.2003, p. 41-46.

Research output: Contribution to journalArticle

Németh, Zoltán H. ; Deitch, Edwin A. ; Szabo, Csaba ; Haskó, György. / Pyrrolidinedithiocarbamate inhibits NF-κB activation and IL-8 production in intestinal epithelial cells. In: Immunology Letters. 2003 ; Vol. 85, No. 1. pp. 41-46.
@article{8a505b5a6e7146fe92c9919618e6a584,
title = "Pyrrolidinedithiocarbamate inhibits NF-κB activation and IL-8 production in intestinal epithelial cells",
abstract = "During inflammatory bowel disease and intestinal ischemia, epithelial cells of the gut mucosa produce various inflammatory mediators, including the chemokine interleukin (IL-8). This IL-8 produced by intestinal epithelial cells has recently been implicated as a contributory factor to the deleterious inflammatory process resulting in colitis during inflammatory bowel disease or multiple organ failure following shock and trauma. Recent evidence suggests that the transcription factor nuclear factor κB (NF-κB) is a central regulator of IL-8 gene expression. In the present paper we investigated the effect of pharmacological inhibition of NF-κB with pyrrolidinedithiocarbamate (PDTC) on IL-1β-induced IL-8 production by the human intestinal epithelial cell line HT-29. Pretreatment of cells with PDTC (3-1000 μM) dose-dependently attenuated IL-8 production. Furthermore, PDTC (100 μM) suppressed the accumulation of IL-8 mRNA. PDTC inhibited the activation of NF-κB, because PDTC suppressed both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Taken together, our data demonstrate that NF-κB inhibition with PDTC decreases IL-8 production by intestinal epithelial cells.",
keywords = "Crohn's disease, Sepsis, Transcription factor",
author = "N{\'e}meth, {Zolt{\'a}n H.} and Deitch, {Edwin A.} and Csaba Szabo and Gy{\"o}rgy Hask{\'o}",
year = "2003",
month = "1",
day = "2",
doi = "10.1016/S0165-2478(02)00208-0",
language = "English (US)",
volume = "85",
pages = "41--46",
journal = "Immunology Letters",
issn = "0165-2478",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Pyrrolidinedithiocarbamate inhibits NF-κB activation and IL-8 production in intestinal epithelial cells

AU - Németh, Zoltán H.

AU - Deitch, Edwin A.

AU - Szabo, Csaba

AU - Haskó, György

PY - 2003/1/2

Y1 - 2003/1/2

N2 - During inflammatory bowel disease and intestinal ischemia, epithelial cells of the gut mucosa produce various inflammatory mediators, including the chemokine interleukin (IL-8). This IL-8 produced by intestinal epithelial cells has recently been implicated as a contributory factor to the deleterious inflammatory process resulting in colitis during inflammatory bowel disease or multiple organ failure following shock and trauma. Recent evidence suggests that the transcription factor nuclear factor κB (NF-κB) is a central regulator of IL-8 gene expression. In the present paper we investigated the effect of pharmacological inhibition of NF-κB with pyrrolidinedithiocarbamate (PDTC) on IL-1β-induced IL-8 production by the human intestinal epithelial cell line HT-29. Pretreatment of cells with PDTC (3-1000 μM) dose-dependently attenuated IL-8 production. Furthermore, PDTC (100 μM) suppressed the accumulation of IL-8 mRNA. PDTC inhibited the activation of NF-κB, because PDTC suppressed both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Taken together, our data demonstrate that NF-κB inhibition with PDTC decreases IL-8 production by intestinal epithelial cells.

AB - During inflammatory bowel disease and intestinal ischemia, epithelial cells of the gut mucosa produce various inflammatory mediators, including the chemokine interleukin (IL-8). This IL-8 produced by intestinal epithelial cells has recently been implicated as a contributory factor to the deleterious inflammatory process resulting in colitis during inflammatory bowel disease or multiple organ failure following shock and trauma. Recent evidence suggests that the transcription factor nuclear factor κB (NF-κB) is a central regulator of IL-8 gene expression. In the present paper we investigated the effect of pharmacological inhibition of NF-κB with pyrrolidinedithiocarbamate (PDTC) on IL-1β-induced IL-8 production by the human intestinal epithelial cell line HT-29. Pretreatment of cells with PDTC (3-1000 μM) dose-dependently attenuated IL-8 production. Furthermore, PDTC (100 μM) suppressed the accumulation of IL-8 mRNA. PDTC inhibited the activation of NF-κB, because PDTC suppressed both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Taken together, our data demonstrate that NF-κB inhibition with PDTC decreases IL-8 production by intestinal epithelial cells.

KW - Crohn's disease

KW - Sepsis

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=0037413481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037413481&partnerID=8YFLogxK

U2 - 10.1016/S0165-2478(02)00208-0

DO - 10.1016/S0165-2478(02)00208-0

M3 - Article

VL - 85

SP - 41

EP - 46

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

IS - 1

ER -