Abdominal irradiation increases inflammatory cytokine expression and activates NF-kappaB in rat ileal muscularis layer.
The small bowel is an important dose-limiting organ in abdominal radiotherapy because irradiation can cause acute enteritis that, in turn, leads to progressively reduced motility and finally, in a later phase, to fibrosis. Because these clinical symptoms may be caused by the early stage of an inflammatory process, we characterized the radiation-induced intestinal inflammation in rats. Abdominal gamma-irradiation (10-Gy) induced a cascade of inflammatory events characterized by an early (6 h after exposure) increase in IL-1beta, TNF-alpha, and IL-6 mRNA levels in the rat ileal muscularis layer. IL-8 [a cytokine-induced neutrophil chemoattractant (CINC)] mRNA appeared later (at 3 days). The expression of TGF-beta (a profibrotic cytokine) was higher in irradiated than control tissue at day 1, whereas IL-10 (an anti-inflammatory cytokine) expression vanished completely. Despite strong IL-1ra expression, the IL-1ra/IL-1beta ratio, which is an indicator of inflammatory balance, was -41% at day 1 in irradiated compared with control tissue. The nuclear transcription factors NF-kappaB and activator protein-1 (AP-1) govern transcription of these genes, directly or indirectly. Although expression of the subunits of NF-kappaB (p65, p50) and AP-1 (c-fos, c-jun) did not increase, irradiation caused a rapid and persistent translocation of p65 and p50. An imbalance between proinflammatory and anti-inflammatory mediators may contribute to perpetuating intestinal inflammation, thus making it chronic.
Linard
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Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection de la santé de l'Homme et de Dosimétrie, IRSN, BP 17, F-92262 Fontenay-aux-Roses Cedex, France. christine.linard@irsn.fr
Ropenga
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Vozenin-Brotons
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MC
Chapel
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Mathe
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D000005:Abdomen / Q000528:radiation effects*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D007082:Ileum / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D020033:Protein Isoforms; D012333:RNA, Messenger; D018808:Transcription Factor AP-1