Induction of interleukin 6 by ionizing radiation in a human epithelial cell line: control by corticosteroids.
The cutaneous radiation syndrome after therapeutic or accidental exposure of human skin to ionizing radiation (IR) is accompanied by inflammatory processes which are controlled partly by proinflammatory cytokines. Besides tumour necrosis factor (TNF)-alpha and interleukin (IL)1, the pluripotent cytokine IL-6 belongs to the key mediators of inflammation. So far, there are no reports about the regulation of IL-6 by IR in epidermal cells. As an in vitro model to study the effects of IR on IL-6 gene expression, we treated the human epithelial HeLa cell line with different single X-ray doses between 1 and 20 Gy. Twenty-four hours after irradiation the IL-6 secretion was dose-dependently enhanced as measured by ELISA. At the transcriptional level, a slight increase of IL-6 transcripts was already detectable 1 h after irradiation, with maximum levels at 2 h, and a decline to baseline levels between 8 and 24 h. Addition of the transcriptional inhibitor actinomycin D inhibited the inducibility of IL-6 mRNA by TPA and IR. As the IL-6 promoter contains multiple binding sites for activated glucocorticoid receptors within the 5' regulatory region, the potential modulation of IL-6 expression by the corticosteroids hydrocortisone, dexamethasone and mometasone furoate was included in our study to modify the radiation-induced stress response. All corticosteroids applied could efficiently downregulate TPA- or radiation-induced IL-6 expression on both gene expression and protein levels. Mometasone furoate, followed by dexamethasone, was found to be most effective at low concentrations (1 nM), whereas hydrocortisone had to be applied at about 100-fold higher concentrations to achieve comparable inhibition. This experimental model is aimed at understanding the molecular circuits following IR, and thus to provide a basis for the treatment of radiation effects in skin.
Beetz
A
A
Department of Dermatology, University of Ulm, Germany.
Messer
G
G
Oppel
T
T
van Beuningen
D
D
Peter
R U
RU
Kind
P
P
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D015854:Up-Regulation / Q000528:radiation effects; D014965:X-Rays
D000305:Adrenal Cortex Hormones; D002273:Carcinogens; D015850:Interleukin-6; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate