PMID- 18077625
OWN - NLM
STAT- MEDLINE
DCOM- 20080324
LR  - 20131121
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Linking)
VI  - 324
IP  - 3
DP  - 2008 Mar
TI  - Reduction of peroxisome proliferation-activated receptor gamma expression by 
      gamma-irradiation as a mechanism contributing to inflammatory response in rat 
      colon: modulation by the 5-aminosalicylic acid agonist.
PG  - 911-20
AB  - Radiation-induced intestinal injuries, including inflammation and immune 
      response, remain a limiting factor in the effectiveness of pelvic radiotherapy 
      and in the patient's quality of life during and after treatment. Peroxisome 
      proliferation-activated receptor (PPAR) agonists are now emerging as therapeutic 
      drugs for various inflammatory diseases that are characterized by impaired PPAR 
      expression. The purpose of this study was to investigate the profile of PPAR 
      expression in rat colonic mucosa 3 and 7 days after abdominal gamma-irradiation 
      (10 Gy). We tested whether irradiation-induced acute inflammatory response could 
      be modulated pharmacologically with the antiinflammatory properties of 
      5-aminosalicylic acid (5-ASA) (250 mg/kg/day), which is a PPAR activator. 
      Irradiation drastically reduced mRNA and protein levels of PPARalpha and -gamma 
      and of the heterodimer retinoid X receptor (RXR)alpha at 3 days postirradiation. 
      5-ASA treatment normalized both PPARgamma and RXRalpha expression at 3 days 
      postirradiation and PPARalpha at 7 days. By promoting PPAR expression and its 
      nuclear translocation, 5-ASA interfered with the nuclear factor (NF)-kappaB 
      pathway, both by reducing irradiation-induced NF-kappaB p65 
      translocation/activation and increasing the expression of nuclear factor-kappaB 
      inhibitor (IkappaB) mRNA and protein. Therefore, 5-ASA prevents 
      irradiation-induced inflammatory processes as well as expression of tumor 
      necrosis factor alpha, monocyte chemotactic protein-1, inducible nitric-oxide 
      synthase, and macrophage infiltration. In addition, 5-ASA restores the interferon 
      gamma/signal transducer and activator of transcription (STAT)-1 and STAT-3 
      concentrations that were impaired at 3 and 7 days postirradiation and are 
      correlated with suppressor of cytokine signaling-3 repression. Collectively, 
      these results indicate that PPAR agonists may be effective in the prevention of 
      inflammatory processes and immune responses during and after pelvic radiotherapy.
FAU - Linard, Christine
AU  - Linard C
AD  - Institut de Radioprotection et de Surete Nucleaire, Direction de la 
      Radioprotection de l'Homme, Laboratoire de Radiopathology, B.P. no. 17, F-92262 
      Fontenay-aux-Roses Cedex, France. christine.linard@irsn.fr
FAU - Gremy, Olivier
AU  - Gremy O
FAU - Benderitter, Marc
AU  - Benderitter M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20071212
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (PPAR gamma)
RN  - 4Q81I59GXC (Mesalamine)
SB  - IM
MH  - Animals
MH  - Colitis/drug therapy/*metabolism/pathology
MH  - Colon/drug effects/metabolism/pathology
MH  - *Gamma Rays
MH  - Gene Expression Regulation/drug effects/physiology/*radiation effects
MH  - Inflammation/drug therapy/metabolism/pathology
MH  - Male
MH  - Mesalamine/*pharmacology/therapeutic use
MH  - PPAR gamma/*agonists/metabolism/*radiation effects
MH  - Rats
MH  - Rats, Wistar
EDAT- 2007/12/14 09:00
MHDA- 2008/03/25 09:00
CRDT- 2007/12/14 09:00
PHST- 2007/12/14 09:00 [pubmed]
PHST- 2008/03/25 09:00 [medline]
PHST- 2007/12/14 09:00 [entrez]
AID - jpet.107.129122 [pii]
AID - 10.1124/jpet.107.129122 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2008 Mar;324(3):911-20. doi: 10.1124/jpet.107.129122. Epub 
      2007 Dec 12.