title: [Mycoplasma genitalium-derived lipid-associated membrane proteins negatively regulate cytokine secretion by inducing HO-1 expression in placental trophoblast cells].
abstract: OBJECTIVE
  To observe the expression of heme oxygenase-1 (HO-1) in regulation of cytokines response induced by Mycoplasma genitalium-derived lipid-associated membrane proteins (LAMPs) in placental trophoblast cells.
  
  
  METHODS
  Placental trophoblast cells were cultured in vitro and stimulated by 0.5-5 μg/mL LAMPs for 4 to 12 hours. Expression of HO-1 mRNA and protein, and nuclear translocation of nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time quantitative PCR and Western blotting, respectively. The intracellular formation of reactive oxygen species (ROS) was detected by the fluorescent probe H2DCFDA. N-acetyl-cysteine (NAC) and nuclear factor erythroid-2 related factor 2 (Nrf2) siRNA were respectively used to analyze the roles of ROS and Nrf2 in mediating HO-1 expression. Finally, placental trophoblast cells were transfected with HO-1 siRNA, or preincubated by the HO-1 agonist cobalt protoporphyrin (CoPP) or its inhibitor zinc protoporphyrin (ZnPP), and LAMPs-induced secretion of TNF-α and IL-1β were detected by ELISA.
  
  
  RESULTS
  M. genitalium LAMPs induced the expression of HO-1 mRNA and protein, the accumulation of ROS and the nuclear translocation of Nrf2 in placental trophoblast cells. NAC treatment inhibited LAMPs-induced HO-1 expression and Nrf2 nuclear translocation, and the transfection of Nrf2 siRNA significantly abrogated HO-1 expression. Furthermore, HO-1 siRNA and ZnPP treatment increased LAMPs-induced TNF-α and IL-1β secretion, while the HO-1 agonist CoPP treatment further decreased their production.
  
  
  CONCLUSIONS
  M. genitalium LAMPs could induce placental trophoblast cells to express HO-1 through ROS/Nrf2 pathways. Up-regulation of HO-1 negatively regulates excessive production of cytokines.
authors: Departments of Gynecology and Obstetrics, First Affiliated Hospital, Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Lu
authors: L
authors: He
authors: Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Xiaoxing
authors: X
authors: You
authors: Institute of Cardiovascular Disease, University of South China, Hengyang 421001, China.
authors: Guohua
authors: G
authors: Li
authors: Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Yanhua
authors: Y
authors: Zeng
authors: Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Ranhui
authors: R
authors: Li
authors: Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Cuiming
authors: C
authors: Zhu
authors: Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Minjun
authors: M
authors: Yu
authors: Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, China.
authors: Yimou
authors: Y
authors: Wu
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009175:Mycoplasma Infections / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology; D045704:Mycoplasma genitalium / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology* / Q000201:enzymology / Q000382:microbiology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1