Induction of manganese superoxide dismutase by tumour necrosis factor-α in human endometrial stromal cells

Abstract

The present study was undertaken to investigate the effect of tumour necrosis factor-α (TNFα) on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC) and to determine whether there is a difference in responsiveness to TNFα between ESC and decidualized ESC. TNFα increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNFα required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNFα had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either type of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibitor, blocked TNFα-induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kinase C (PKC), also inhibited TNFα-stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNFα-induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dependent phosphorylation and that de-novo protein synthesis is not required for the TNFα effect. In summary, TNFα induces Mn-SOD expression in human ESC. This phenomenon may be important for protectionof ESC from cytokine-mediated oxidative stress. © 2001 European Society of Human Reproduction and Embryology.