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

• Published in: Molecular human reproduction 2001-11, Vol.7 (11), p.1065-1072
• Main Authors: Karube-Harada, Ayako, Sugino, Norihiro, Kashida, Shiro, Takiguchi, Shuji, Takayama, Hisako, Yamagata, Yoshiaki, Nakamura, Yasuhiko, Kato, Hiroshi
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Adult; Biological and medical sciences; Cells, Cultured; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Dose-Response Relationship, Drug; Embryo Implantation; endometrial stromal cells; Endometrium - cytology; Endometrium - drug effects; Endometrium - physiology; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Humans; Mammalian female genital system; Middle Aged; protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - drug effects; Protein Kinase C - metabolism; Protein Synthesis Inhibitors - pharmacology; Stromal Cells - drug effects; Stromal Cells - metabolism; superoxide dismutase; Superoxide Dismutase - drug effects; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; superoxide radical; Tetradecanoylphorbol Acetate - pharmacology; TNFα; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: reproduction
• ISSN: 1360-9947; 1460-2407; 1460-2407
• DOI: 10.1093/molehr/7.11.1065

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 protection of ESC from cytokine-mediated oxidative stress.