NF-kappaB and AP-1 are responsible for inducibility of the IL-6 promoter by ionizing radiation in HeLa cells.
Int J Radiat Biol
; 76(11): 1443-53, 2000 Nov.
Article
in En
| MEDLINE
| ID: mdl-11098847
ABSTRACT
PURPOSE:
To investigate the mechanisms leading to initiation by ionizing radiation of IL-6 transcription in HeLa cells. MATERIALS ANDMETHODS:
HeLa cells were irradiated with X-rays at a dose rate of approximately 1 Gy/min or treated with TPA (100 ng/ml). Transient transfection analysis with truncated IL-6 promoter CAT constructs was used to identify the radiation-sensitive region within the IL-6 promoter/enhancer.RESULTS:
For basal expression of the IL-6 gene in unirradiated control cells the presence of the binding site for the nuclear factor kappa B (NF-kappaB) and the multiple response elements (MRE) were necessary. After deletion of either the activator protein (AP)-1 or the MRE site, radiation-induced IL-6 promoter CAT activity was significantly reduced, whereas after deletion of the NF-kappaB site it was completely abolished. Maximal radiation-induced IL-6 promoter CAT activity was observed when the AP-1, NF-kappaB and MRE motifs were present. In electrophoretic mobility shift analyses (EMSA), X-ray-inducible activity was found for NF-kappaB and AP-1 at the MRE constitutive, but no inducible activities were detectable. The nuclear factor IL-6 (NF-IL6) element showed no specific radiation-responsive activity.CONCLUSIONS:
These results demonstrate that NF-kappaB plays a major role in X-ray-inducible IL-6 expression in HeLa cells. The fact that IL-6 promoter activity was dramatically enhanced in the presence of the MRE and distal AP-1 binding motif is indicative of a cooperative mode of transcriptional activation involving all three transcription factor systems. These data provide new insights into the prodromal events of radiation-induced inflammation of epithelial cells and putatively the cutaneous radiation syndrome.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
NF-kappa B
/
Interleukin-6
/
Promoter Regions, Genetic
/
Transcription Factor AP-1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Int J Radiat Biol
Journal subject:
RADIOLOGIA
Year:
2000
Document type:
Article
Affiliation country: