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 language | English (US) |
|---|---|
| Pages (from-to) | 41-46 |
| Number of pages | 6 |
| Journal | Immunology Letters |
| Volume | 85 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2 2003 |
| Externally published | Yes |
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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 journal › Article
}
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
C2 - 12505195
AN - SCOPUS:0037413481
VL - 85
SP - 41
EP - 46
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 1
ER -