Abdominal irradiation increases inflammatory cytokine expression and activates NF-κB in rat ileal muscularis layer
| Autor: | Christine Linard, Denis Mathé, A. Ropenga, A. Chapel, Marie-Catherine Vozenin-Brotons |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Pathology medicine.medical_specialty Physiology medicine.medical_treatment Motility Inflammation Biology Enteritis chemistry.chemical_compound Ileum Physiology (medical) Abdomen medicine Animals Protein Isoforms RNA Messenger Rats Wistar Hepatology NF-kappa B Gastroenterology Muscle Smooth NF-κB NFKB1 medicine.disease Small intestine Rats Transcription Factor AP-1 Cytokine medicine.anatomical_structure chemistry Cytokines Inflammation Mediators medicine.symptom |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1522-1547 0193-1857 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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