PMID- 18645606
OWN - NLM
STAT- MEDLINE
DCOM- 20081001
LR  - 20211020
IS  - 1449-1907 (Electronic)
IS  - 1449-1907 (Linking)
VI  - 5
IP  - 4
DP  - 2008 Jul 3
TI  - Infliximab and etanercept are equally effective in reducing enterocyte APOPTOSIS 
      in experimental colitis.
PG  - 169-80
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-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.
FAU - Fries, Walter
AU  - Fries W
AD  - Dipartimento di Medicina Interna e Terapia Medica, Sezione di Farmacologia, 
      Universita di Messina, Messina, Italy. fwalter@unime.it
FAU - Muja, Carmelo
AU  - Muja C
FAU - Crisafulli, Carmela
AU  - Crisafulli C
FAU - Costantino, Giuseppe
AU  - Costantino G
FAU - Longo, Giuseppe
AU  - Longo G
FAU - Cuzzocrea, Salvatore
AU  - Cuzzocrea S
FAU - Mazzon, Emanuela
AU  - Mazzon E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080703
PL  - Australia
TA  - Int J Med Sci
JT  - International journal of medical sciences
JID - 101213954
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Benzenesulfonates)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 12379-41-8 (dinitrobenzenesulfonic acid)
RN  - B72HH48FLU (Infliximab)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Benzenesulfonates
MH  - Blotting, Western
MH  - Colitis/chemically induced/drug therapy/*physiopathology
MH  - Disease Models, Animal
MH  - Enterocytes/*drug effects/metabolism/pathology
MH  - Etanercept
MH  - Fas Ligand Protein/metabolism
MH  - Immunoglobulin G/*pharmacology
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Infliximab
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Tumor Necrosis Factor
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/physiology
MH  - Tumor Necrosis Factor-alpha/blood
PMC - PMC2452978
OTO - NOTNLM
OT  - Apoptosis
OT  - Enterocyte
OT  - Experimental Colitis
OT  - TNF-alpha
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2008/07/23 09:00
MHDA- 2008/10/02 09:00
PMCR- 2008/01/01
CRDT- 2008/07/23 09:00
PHST- 2008/03/30 00:00 [received]
PHST- 2008/07/01 00:00 [accepted]
PHST- 2008/07/23 09:00 [pubmed]
PHST- 2008/10/02 09:00 [medline]
PHST- 2008/07/23 09:00 [entrez]
PHST- 2008/01/01 00:00 [pmc-release]
AID - ijmsv05p0169 [pii]
AID - 10.7150/ijms.5.169 [doi]
PST - epublish
SO  - Int J Med Sci. 2008 Jul 3;5(4):169-80. doi: 10.7150/ijms.5.169.