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Radioprotection of Murine Gastrointestinal Epithelium by Interleukin-1 alpha Involves Down-regulation of the Apoptotic Response

  作者 Johnke, RM; Smith, ES; Cariveau, MJ; Evans, MJ; Kilburn, JM; Bakken, NTG; Nangami, GN  
  选自 期刊  Anticancer Research;  卷期  2008年28-6A;  页码  3601-3607  
  关联知识点  
 

[摘要]Background: Interleukin-1 alpha (IL-1) is known to radioprotect the gastrointestinal tract, but the mechanism by which this protection occurs remains unclear. These studies were undertaken to investigate whether the radioprotective potential of IL-1 may be linked to an ability to reduce apoptosis within the gastrointestinal crypts. Materials and Methods: IL-1 was administered to C57Bl/6 mice 24 hours prior to receiving 8 Gy abdominal X-irradiation (xRT). At designated times, experimental mice were sacrificed, jejunal tissue removed, and paraffin-embedded sections analyzed for apoptosis indices (AI) and immunohistochemical determination of active caspase-3, -8 and -9. Results: AI data demonstrated that 8 Gy irradiation resulted in a marked jejunal apoptotic response, but IL-1 pretreatment significantly attenuated this response. Concomitant with this attenuation, reduced levels of caspase-3 and 9, but not caspase-8, activation were observed, particularly within goblet cells. Conclusion: The results outlined herein suggest that radioprotection by IL-1 is mediated, at least in part, through a reduction in the apoptotic response which appears to involve down-regulation of the intrinsic apoptotic pathway.

 
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