Early induction of the II-5 promotor activity and IL-6 by ionizing radiation in human cell lines

Recently there is increasing evidence that the effects of ionizing radiation are not exclusively confined to inhibition of proliferative activity. Several cytokines and -receptors, such as TNF and EGF-Receptor have been demonstrated to be upregulted in lymphoid and epidermal cell lines, respectively. Here we report on two other cytokines with a central role in inflammatory reactions. By transfecting IL-5 and IL-6 promotor constructs into the Jurkat and HeLa cell lines, respectively, as well as by Northern analysis and ELISA, a distinct inducibility of IL-5 and II-6 promotor-CAT reporter gene activity could be determined following single X-ray doses between 1 and 10 Gy for both cytokines, showing the maximum of the RNA induction for IL-6 at 2 hrs. and for IL-6 protein at 24 hrs. Radiation-induced induction of IL-5 reporter gene activity can be antagonized by Cyclosporin A, induction of IL-6 by the steroids Hydrocortisone, Dexamethasone, and Mometasonefurorate, demonstrating the best effect for Mometasonfurorate. The data demonstrate that ionizing radiation leads, apart from TNF, to induction and post transcriptional mechanisms. As these effects can be observed in a therapeutical dose range between 1 and 4 Gy, they may be useful for developing new radiation fractionation protocols in cancer therapy. Additionally, it has been shown that these cytokines are susceptible to regulatory effects of steroids and the immunosuppressant Cyclosporin A