Limits...
Infliximab and etanercept are equally effective in reducing enterocyte APOPTOSIS in experimental colitis.

Fries W, Muja C, Crisafulli C, Costantino G, Longo G, Cuzzocrea S, Mazzon E - Int J Med Sci (2008)

Bottom Line: Circulating TNF-alpha levels were effectively reduced by IFX and ETC (p<0.01, both) at 3 and 6 h.These alterations were prevented by both anti-TNF strategies, and in TNFR-1(-/-) animals.Both anti-TNF strategies, IFX and ETC, were equally effective in suppressing enterocyte apoptosis, most likely by inactivation of circulating TNF-alpha.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Medicina Interna e Terapia Medica, Sezione di Farmacologia, Università di Messina, Messina, Italy. fwalter@unime.it

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-alpha (TNF-alpha), 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-alpha levels were effectively reduced by IFX and ETC (p<0.01, both) at 3 and 6 h. Apoptosis of the ileal enterocytes, assessed by TUNEL staining, staining for Fas-ligand, and bax, increased at 3 and 6h. These alterations were prevented by both anti-TNF strategies, and in TNFR-1(-/-) 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-alpha.

Show MeSH

Related in: MedlinePlus

Tunel staining at 3 h (left column) at 6 h (right column) in control ilea (A,B) showing no positivity except for isolated enterocytes at both time-points; positivity (arrowheads) appeared 3 h (B) after colitis induction with DNB/ethanol along the villus axis and increased at 6 h (C); positivity of Tunel staining was completely prevented by treatment with ETC (5 mg/kg s.c.) (E,F) and with IFX (G,H), and in TNFR-1-/- mice (I,J).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2452978&req=5

Figure 1: Tunel staining at 3 h (left column) at 6 h (right column) in control ilea (A,B) showing no positivity except for isolated enterocytes at both time-points; positivity (arrowheads) appeared 3 h (B) after colitis induction with DNB/ethanol along the villus axis and increased at 6 h (C); positivity of Tunel staining was completely prevented by treatment with ETC (5 mg/kg s.c.) (E,F) and with IFX (G,H), and in TNFR-1-/- mice (I,J).

Mentions: Isolated positivity was observed at any time-point in control ilea on TUNEL staining (fig.1), nor in sham colitis treated with ETC or IFX. Three hours after colitis induction a few cells distributed along the entire length of the villi stained positive (fig. 1 C). At 6 h, the number of apoptotic cells had increased (fig. 1 D). No TUNEL-positive cells were observed at either time-points with either treatment, ETC or IFX (fig. 1 E-H), nor in TNFR-1-/- mice (fig. 1 I,J).


Infliximab and etanercept are equally effective in reducing enterocyte APOPTOSIS in experimental colitis.

Fries W, Muja C, Crisafulli C, Costantino G, Longo G, Cuzzocrea S, Mazzon E - Int J Med Sci (2008)

Tunel staining at 3 h (left column) at 6 h (right column) in control ilea (A,B) showing no positivity except for isolated enterocytes at both time-points; positivity (arrowheads) appeared 3 h (B) after colitis induction with DNB/ethanol along the villus axis and increased at 6 h (C); positivity of Tunel staining was completely prevented by treatment with ETC (5 mg/kg s.c.) (E,F) and with IFX (G,H), and in TNFR-1-/- mice (I,J).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2452978&req=5

Figure 1: Tunel staining at 3 h (left column) at 6 h (right column) in control ilea (A,B) showing no positivity except for isolated enterocytes at both time-points; positivity (arrowheads) appeared 3 h (B) after colitis induction with DNB/ethanol along the villus axis and increased at 6 h (C); positivity of Tunel staining was completely prevented by treatment with ETC (5 mg/kg s.c.) (E,F) and with IFX (G,H), and in TNFR-1-/- mice (I,J).
Mentions: Isolated positivity was observed at any time-point in control ilea on TUNEL staining (fig.1), nor in sham colitis treated with ETC or IFX. Three hours after colitis induction a few cells distributed along the entire length of the villi stained positive (fig. 1 C). At 6 h, the number of apoptotic cells had increased (fig. 1 D). No TUNEL-positive cells were observed at either time-points with either treatment, ETC or IFX (fig. 1 E-H), nor in TNFR-1-/- mice (fig. 1 I,J).

Bottom Line: Circulating TNF-alpha levels were effectively reduced by IFX and ETC (p<0.01, both) at 3 and 6 h.These alterations were prevented by both anti-TNF strategies, and in TNFR-1(-/-) animals.Both anti-TNF strategies, IFX and ETC, were equally effective in suppressing enterocyte apoptosis, most likely by inactivation of circulating TNF-alpha.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Medicina Interna e Terapia Medica, Sezione di Farmacologia, Università di Messina, Messina, Italy. fwalter@unime.it

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-alpha (TNF-alpha), 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-alpha levels were effectively reduced by IFX and ETC (p<0.01, both) at 3 and 6 h. Apoptosis of the ileal enterocytes, assessed by TUNEL staining, staining for Fas-ligand, and bax, increased at 3 and 6h. These alterations were prevented by both anti-TNF strategies, and in TNFR-1(-/-) 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-alpha.

Show MeSH
Related in: MedlinePlus