ANTICANCER AGENT OK432 INDUCES MANGANESE SUPEROXIDE-DISMUTASE IN HUMAN GRANULOCYTES

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme invol ved in scavenging O-2(-). OK432, a Streptococcol preparation, has anti -tumor activity and is also known to be a biological-response modifier . In this study, we have examined the regulation of MnSOD gene by OK43 2 in human granulocytes. Granulocytes had a low activity of MnSOD; OK4 32 increased MnSOD mRNA levels in a dose-dependent manner and its acti vity in granulocytes. OK432 also induced the MnSOD mRNA in HL60 promye locytes, while not affecting the levels of MnSOD mRNA in human fibrobl asts. Pre-treatment with either actinomycin D or cycloheximide inhibit ed the induction of MnSOD mRNA by OK432. OK432 increased the levels of interleukin-1 (IL-1) and tumor-necrosis-factor-alpha (TNF alpha) mRNA in granulocytes. Furthermore, the induction of MnSOD mRNA by OK432 wa s blocked by anti-lL-1 antibody but not by anti-TNF antibody. These re sults suggest that the induction of MnSOD mRNA by OK432 is regulated a t the transcriptional level, and OK432 induces MnSOD mRNA, at least in part, through production of IL-1 in granulocytes. (C) 1996 Wiley-Liss , Inc.