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

The present study was undertaken to investigate the effect of tumour necros is factor-alpha (TNF alpha) on superoxide dismutase (SOD) expression in hum an endometrial stromal cells (ESC) and to determine whether there is a diff erence in responsiveness to TNF alpha between ESC and decidualized ESC. TNF alpha increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNF alpha required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNF alpha had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either ty pe of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibito r, blocked TNF alpha -induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kin ase C (PKC), also inhibited TNF alpha -stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNF alpha -induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dep endent phosphorylation and that de-novo protein synthesis is not required f or the TNF alpha effect. In summary, TNF alpha induces Mn-SOD expression in human ESC. This phenomenon may be important for protection of ESC from cyt okine-mediated oxidative stress.