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GADD45γ regulates TNF-α and IL-6 synthesis in THP-1 cells

Authors
Shin, GT; Lee, HJ; Kim, H
Citation
Inflammation research : official journal of the European Histamine Research Society, 61(11):1195-1202, 2012
Journal Title
Inflammation research : official journal of the European Histamine Research Society
ISSN
1023-38301420-908X
Abstract
OBJECTIVE AND DESIGN: 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.
MeSH terms
Cell LineCells, CulturedGene Knockdown TechniquesHumansInterleukin-6/*geneticsIntracellular Signaling Peptides and Proteins/*geneticsLeukocytes, Mononuclear/metabolismLipopolysaccharidesRNA, Messenger/metabolismTumor Necrosis Factor-alpha/*genetics
DOI
10.1007/s00011-012-0515-x
PMID
22752116
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Nephrology
AJOU Authors
신, 규태김, 흥수
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