p53-dependent X-ray-induced modulation of cytokine mRNA levels in vivo.
In vitro studies have shown that ionizing radiation can cause increases in some cytokine mRNA levels and activation of the nuclear NF-kappa B and/or AP1 transcription factors which have been implicated in the transcriptional regulation of many cytokine genes. Thus, radiation-induced upregulation of cytokine mRNAs appeared to be in part a direct consequence of transcription factor activation. To test this in vitro model in vivo, the effects of whole-body X-irradiation (0-10 Gy) on cytokine and other gene mRNA levels have been examined in mice. Increases and decreases in cytokine mRNA levels were detected in tissues which underwent an early wave of apoptosis (bone marrow and/or spleen), but not in more radioresistant tissues (kidney, liver, brain, and heart). Some mouse strain-specific differences were observed, but none of the changes in mRNA level was detected in p53-/- mice. As activation of the NF-kappa B and AP1 transcription factors was not detected in early-(spleen) or late-(liver) responding tissues in 10 Gy X-irradiated p53+/+ mice in vivo, it is concluded that the modulation of cytokine gene expression in vivo is p53-dependent and indirectly associated with apoptosis.
Kerr
N C
NC
MRC Radiation and Genome Stability Unit, Chilton, Didcot, Oxon, U.K.
Wright
E G
EG
Plumb
M A
MA
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects; D016207:Cytokines / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects; D014157:Transcription Factors / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53