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

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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.

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Authors and Affiliations

  1. Department of Nephrology, Ajou University School of Medicine, Youngtong-gu, Wonchon-dong, San 5, Suwon, 443-721, Republic of Korea

    Gyu-Tae Shin, Hwa Joung Lee & Heungsoo Kim

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  1. Gyu-Tae Shin
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  2. Hwa Joung Lee
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  3. Heungsoo Kim
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Correspondence to Gyu-Tae Shin.

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Responsible Editor: Graham Wallace.

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Shin, GT., Lee, H.J. & Kim, H. GADD45γ regulates TNF-α and IL-6 synthesis in THP-1 cells. Inflamm. Res. 61, 1195–1202 (2012). https://doi.org/10.1007/s00011-012-0515-x

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  • DOI: https://doi.org/10.1007/s00011-012-0515-x

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