Gyu-Tae Shin1, Hwa Joung Lee, Heungsoo Kim. 1. Department of Nephrology, Ajou University School of Medicine, Youngtong-gu, Wonchon-dong, San 5, Suwon 443-721, Republic of Korea. gtshin@ajou.ac.kr
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.
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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