title: Anti-apoptotic effects of SERPIN B3 and B4 via STAT6 activation in macrophages after infection with Toxoplasma gondii.
abstract: Toxoplasma gondii penetrates all kinds of nucleated eukaryotic cells but modulates host cells differently for its intracellular survival. In a previous study, we found out that serine protease inhibitors B3 and B4 (SERPIN B3/B4 because of their very high homology) were significantly induced in THP-1-derived macrophages infected with T. gondii through activation of STAT6. In this study, to evaluate the effects of the induced SERPIN B3/B4 on the apoptosis of T. gondii-infected THP-1 cells, we designed and tested various small interfering (si-) RNAs of SERPIN B3 or B4 in staurosporine-induced apoptosis of THP-1 cells. Anti-apoptotic characteristics of THP-1 cells after infection with T. gondii disappeared when SERPIN B3/B4 were knock-downed with gene specific si-RNAs transfected into THP-1 cells as detected by the cleaved caspase 3, poly-ADP ribose polymerase and DNA fragmentation. This anti-apoptotic effect was confirmed in SERPIN B3/B4 overexpressed HeLa cells. We also investigated whether inhibition of STAT6 affects the function of SERPIN B3/B4, and vice versa. Inhibition of SERPIN B3/B4 did not influence STAT6 expression but SERPIN B3/B4 expression was inhibited by STAT6 si-RNA transfection, which confirmed that SERPIN B3/B4 was induced under the control of STAT6 activation. These results suggest that T. gondii induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected THP-1 cells for longer survival of the intracellular parasites themselves.
authors.affiliation: The Catholic Institute of Parasitic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Kyoung Ju
authors.initials: KJ
authors.lastname: Song
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Ho-Woo
authors.initials: HW
authors.lastname: Nam
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002460:Cell Line; D053938:DNA Fragmentation; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000235:genetics / Q000502:physiology*; D014123:Toxoplasmosis / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000503:physiopathology*
chemical_list: D000951:Antigens, Neoplasm; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015843:Serpins; C051072:squamous cell carcinoma-related antigen