Irradiation increases manganese superoxide dismutase gene in human fibroblasts. Possible mechanisms for its accumulation

Fibroblasts are one of the mesenchymal cells and constitute a major element of components in bone marrow stroma as well as submucosal and subcutaneous tissue. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme involved in scavenging of superoxide radicals (O2-). In this study, we examined the regulation of MnSOD gene by irradiation in WI38 human fibroblasts. We found that fibroblasts constitutively produced MnSOD; irradiation significantly increased the activity of MnSOD. The increase in MnSOD transcripts by irradiation was both time- and dose-dependent. Pretreatment with cycloheximide, a protein synthesis inhibitor, did not change accumulation of MnSOD mRNA by irradiation. WI38 fibroblasts constitutively produce low levels of IL-1. Induction of MnSOD mRNA by irradiation was blocked by anti-IL-1 antibodies. Inhibition of the cyclooxygenase pathway with indomethacin caused augmentation in the irradiation-induced MnSOD mRNA. These results suggest that induction of MnSOD gene after irradiation is regulated, at least in part, by IL-1 production, and increased levels of MnSOD transcripts also occur through a pathway of prostaglandin inhibition. (author)