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


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.


CONCLUSIONS
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.
Johnke
Roberta M
RM
Department of Radiation Oncology, East Carolina University Brody School of Medicine, Greenville, North Carolina 27834, USA. tracyr@ecu.edu
Smith
Elizabeth S
ES
Cariveau
Mickael J
MJ
Evans
Mark J
MJ
Kilburn
Jeremy M
JM
Bakken
Nicholas T G
NT
Nangami
Gladys N
GN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D005260:Female; D066298:In Vitro Techniques; D053582:Interleukin-1alpha / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D053582:Interleukin-1alpha; D007527:Isoenzymes; D011837:Radiation-Protective Agents; D020169:Caspases