Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

被引:111
作者
Ong, Zhi Yi [2 ]
Gibson, Rachel J. [1 ]
Bowen, Joanne M. [2 ]
Stringer, Andrea M. [2 ]
Darby, Jocelyn M. [2 ]
Logan, Richard M. [3 ]
Yeoh, Ann S. J. [2 ]
Keefe, Dorothy M. [4 ]
机构
[1] Univ Adelaide, Sch Med Sci, Adelaide, SA, Australia
[2] Univ Adelaide, Sch Med, Adelaide, SA, Australia
[3] Univ Adelaide, Sch Dent, Adelaide, SA, Australia
[4] Canc Council S Australia, Eastwood, SA, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
FACTOR-KAPPA-B; INTESTINAL DAMAGE; IRINOTECAN; INTERLEUKIN-11; METHOTREXATE; PATHOBIOLOGY; PREVENTION; MECHANISMS; EXPRESSION; APOPTOSIS;
D O I
10.1186/1748-717X-5-22
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods: Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1 beta, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1 beta, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results: Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1 beta, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions: Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.
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页数:8
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