title: [Role of auto-secreted interferon α in all-trans retinoic acid-induced expression of RIG-G gene].
abstract: OBJECTIVE
  To explore the relationship between interferon (IFN) α and all-trans retinoic acid (ATRA)-induced signaling pathways in the expression of retinoic acid-induced gene G (RIG-G).
  
  
  METHODS
  Acute promyelocytic leukemia cell line NB4 and signal transducer and activator of transcription (STAT)1-deficient U3A cells were used. The protein levels of tyrosine-phosphorylated STAT2 in ATRA-treated NB4 cells were detected by Western blot. The culture supernatants of NB4 cells treated with ATRA for different time or U3A cells transfected with interferon regulatory factor (IRF)-1 were respectively collected. And the concentration of IFN-α was determined by enzyme-linked immunosorbent assay (ELISA). The effects of NB4 cell culture supernatants on the phosphorylation of STAT2 and the expression of RIG-G were detected by Western blot.
  
  
  RESULTS
  The level of phosphorylated-STAT2 was obviously up-regulated in NB4 cells treated with ATRA for 72 hours, as well as the concentration of IFN-α in culture supernatants. The concentration of IFN-α increased from (1.5 ± 0.5) pg/ml in the untreated group to (7.6 ± 0.3) pg/ml (P < 0.05). After a 96-hour treatment, the concentration of IFN-α was up to (63.8 ± 5.8) pg/ml. And these culture supernatants could induce the tyrosine phosphorylation of STAT2 and up-regulate the protein level of RIG-G. As for U3A cells transfected with IRF-1, the concentration of IFN-α from the culture supernatant also increased 3-fold versus the control group transfected with empty vectors [(8.8 ± 1.4) pg/ml vs (3.4 ± 0.4) pg/ml, P < 0.05].
  
  
  CONCLUSIONS
  RIG-G gene expression is closely correlated with the cross-talk between ATRA and IFN-α-induced signaling pathways. ATRA increases the secretion of IFN-α by up-regulating the protein level of IRF-1. Then the secreted IFN-α may induce the phosphorylation of STAT2 and reinforce the expression of RIG-G.
authors.affiliation: Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ye-jiang
authors.initials: YJ
authors.lastname: Lou
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Pan
authors.forename: Gui-ping
authors.initials: GP
authors.lastname: Xu
authors.forename: Li-kun
authors.initials: LK
authors.lastname: Zhuang
authors.forename: Pei-min
authors.initials: PM
authors.lastname: Jia
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Tong
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C116468:IFIT3 protein, human; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D014212:Tretinoin