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GADD45γ regulates TNF-α and IL-6 synthesis in THP-1 cells.
MedLine Citation:
PMID:  22752116     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Gyu-Tae Shin; Hwa Joung Lee; Heungsoo Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-1
Journal Detail:
Title:  Inflammation research : official journal of the European Histamine Research Society ... [et al.]     Volume:  -     ISSN:  1420-908X     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508160     Medline TA:  Inflamm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Nephrology, Ajou University School of Medicine, Youngtong-gu, Wonchon-dong, San 5, Suwon, 443-721, Republic of Korea, gtshin@ajou.ac.kr.
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