Abstract
Loss of epithelial barrier integrity is considered an early step in the pathogenesis of Crohn's disease (CD), and the rate of enterocyte apoptosis is one of the determinants of the intestinal barrier function. Tumor necrosis factor-α (TNF-α), one of the major proinflammatory mediators in CD, is one of the extrinsic signals which initiate apoptosis of enterocytes. The aim of this study was to investigate the early effects of experimental colitis on enterocyte apoptosis, and the effects of two anti-TNF treatments, infliximab (IFX) and etanercept (ETC). In addition, the importance of receptor I for TNF was tested in TNFR-1 -/- mice. Circulating TNF-α levels were effectively reduced by IFX and ETC (p-/- animals. The anti-apoptotic protein Bcl-2 was expressed in the ileal epithelium under control conditions, but was suppressed in DNB-colitis. Expression of Bcl-2 was maintained in both anti-TNF treatments and TNFR-1 -/- mice. DNB colitis induced a very early, rapid increase of enterocyte apoptosis. Both anti-TNF strategies, IFX and ETC, were equally effective in suppressing enterocyte apoptosis, most likely by inactivation of circulating TNF-α.
| Original language | English |
|---|---|
| Pages (from-to) | 169-180 |
| Number of pages | 12 |
| Journal | International Journal of Medical Sciences |
| Volume | 5 |
| Issue number | 4 |
| Publication status | Published - Jul 3 2008 |
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Keywords
- Apoptosis
- Enterocyte
- Experimental colitis
- TNF-α
ASJC Scopus subject areas
- Medicine(all)
Cite this
Infliximab and etanercept are equally effective in reducing enterocyte apoptosis in experimental colitis. / Fries, Walter; Muja, Carmelo; Crisafulli, Carmela; Costantino, Giuseppe; Longo, Giuseppe; Cuzzocrea, Salvatore; Mazzon, Emanuela.
In: International Journal of Medical Sciences, Vol. 5, No. 4, 03.07.2008, p. 169-180.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Infliximab and etanercept are equally effective in reducing enterocyte apoptosis in experimental colitis
AU - Fries, Walter
AU - Muja, Carmelo
AU - Crisafulli, Carmela
AU - Costantino, Giuseppe
AU - Longo, Giuseppe
AU - Cuzzocrea, Salvatore
AU - Mazzon, Emanuela
PY - 2008/7/3
Y1 - 2008/7/3
N2 - Loss of epithelial barrier integrity is considered an early step in the pathogenesis of Crohn's disease (CD), and the rate of enterocyte apoptosis is one of the determinants of the intestinal barrier function. Tumor necrosis factor-α (TNF-α), one of the major proinflammatory mediators in CD, is one of the extrinsic signals which initiate apoptosis of enterocytes. The aim of this study was to investigate the early effects of experimental colitis on enterocyte apoptosis, and the effects of two anti-TNF treatments, infliximab (IFX) and etanercept (ETC). In addition, the importance of receptor I for TNF was tested in TNFR-1 -/- mice. Circulating TNF-α levels were effectively reduced by IFX and ETC (p-/- animals. The anti-apoptotic protein Bcl-2 was expressed in the ileal epithelium under control conditions, but was suppressed in DNB-colitis. Expression of Bcl-2 was maintained in both anti-TNF treatments and TNFR-1 -/- mice. DNB colitis induced a very early, rapid increase of enterocyte apoptosis. Both anti-TNF strategies, IFX and ETC, were equally effective in suppressing enterocyte apoptosis, most likely by inactivation of circulating TNF-α.
AB - Loss of epithelial barrier integrity is considered an early step in the pathogenesis of Crohn's disease (CD), and the rate of enterocyte apoptosis is one of the determinants of the intestinal barrier function. Tumor necrosis factor-α (TNF-α), one of the major proinflammatory mediators in CD, is one of the extrinsic signals which initiate apoptosis of enterocytes. The aim of this study was to investigate the early effects of experimental colitis on enterocyte apoptosis, and the effects of two anti-TNF treatments, infliximab (IFX) and etanercept (ETC). In addition, the importance of receptor I for TNF was tested in TNFR-1 -/- mice. Circulating TNF-α levels were effectively reduced by IFX and ETC (p-/- animals. The anti-apoptotic protein Bcl-2 was expressed in the ileal epithelium under control conditions, but was suppressed in DNB-colitis. Expression of Bcl-2 was maintained in both anti-TNF treatments and TNFR-1 -/- mice. DNB colitis induced a very early, rapid increase of enterocyte apoptosis. Both anti-TNF strategies, IFX and ETC, were equally effective in suppressing enterocyte apoptosis, most likely by inactivation of circulating TNF-α.
KW - Apoptosis
KW - Enterocyte
KW - Experimental colitis
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=47349097005&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47349097005&partnerID=8YFLogxK
M3 - Article
VL - 5
SP - 169
EP - 180
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
SN - 1449-1907
IS - 4
ER -