Radioprotection of murine gastrointestinal epithelium by interleukin-1alpha involves down-regulation of the apoptotic response.

Autor: Johnke RM; Department of Radiation Oncology, East Carolina University Brody School of Medicine, Greenville, North Carolina 27834, USA. tracyr@ecu.edu, Smith ES, Cariveau MJ, Evans MJ, Kilburn JM, Bakken NT, Nangami GN
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2008 Nov-Dec; Vol. 28 (6A), pp. 3601-7.
Abstrakt: Background: Interleukin-1alpha (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.
Databáze: MEDLINE