title: GADD45γ regulates TNF-α and IL-6 synthesis in THP-1 cells.
abstract: OBJECTIVE
  This study investigated the link between growth arrest and DNA damage 45γ (GADD45γ) expression and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) synthesis.
  
  
  METHODS
  We stimulated THP-1 monocyte cells using lipopolysaccharide (LPS). We knocked-down and over-expressed GADD45γ using lentiviral vectors harboring GADD45γ short hairpin RNA and GADD45γ open reading frame, respectively. To inhibit activation of c-Jun-terminal kinase (JNK), we used a specific inhibitor, SP600125.
  
  
  RESULTS
  LPS stimulation of THP-1 cells resulted in increased expression of GADD45γ mRNA which reached its peak 2 h after stimulation and gradually diminished thereafter. TNF-α and IL-6 were up-regulated at both the mRNA and protein levels in activated THP-1 cells. Knock-down of GADD45γ reduced TNF-α protein production by up to 75 % and IL-6 protein by up to 60 %. In contrast, over-expression of GADD45γ increased TNF-α production by six-fold and IL-6 protein by 80-fold. There was a discrepancy between TNF-α mRNA and its protein level, whereas IL-6 mRNA and its protein level were correlated. Knock-down of GADD45γ decreased the JNK activity, suggesting that JNK may play the role of a downstream mediator for the pro-inflammatory effects of GADD45γ.
  
  
  CONCLUSIONS
  We show evidence that GADD45γ may regulate TNF-α and IL-6 expression in activated THP-1 monocyte cells.
authors: Department of Nephrology, Ajou University School of Medicine, Youngtong-gu, Wonchon-dong, San 5, Suwon 443-721, Republic of Korea. gtshin@ajou.ac.kr
authors: Gyu-Tae
authors: GT
authors: Shin
authors: Hwa Joung
authors: HJ
authors: Lee
authors: Heungsoo
authors: H
authors: Kim
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D000097642:GADD45 Proteins
chemical_list: D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C485654:GADD45G protein, human; D000097642:GADD45 Proteins