Document Detail

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes.
MedLine Citation:
PMID:  23241898     Owner:  NLM     Status:  MEDLINE    
Toll-like receptors (TLRs) are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbial recognition by TLRs and subsequent TLR-triggered cytokine production are deregulated. Activating transcription factor 4 (ATF4), a member of the ATF/CREB transcription factor family, is an important factor that participates in several pathophysiological processes. In this report, we found that ATF4 is also involved in the TLR-mediated innate immune response, which participates in TLR4 signal transduction and mediates the secretion of a variety of cytokines. We observed that ATF4 is activated and translocates to the nucleus following lipopolysaccharide (LPS) stimulation via the TLR4-MyD88-dependent pathway. Additionally, a cytokine array assay showed that some key inflammatory cytokines, such as IL-6, IL-8 and RANTES, are positively regulated by ATF4. We also demonstrate that c-Jun directly binds to ATF4, thereby promoting the secretion of inflammatory cytokines. Taken together, these results indicate that ATF4 acts as a positive regulator in TLR4-triggered cytokine production.
Chunyan Zhang; Nan Bai; Antao Chang; Zhuhong Zhang; Jing Yin; Wenzhi Shen; Yaping Tian; Rong Xiang; Chenghu Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-17
Journal Detail:
Title:  Cellular & molecular immunology     Volume:  10     ISSN:  2042-0226     ISO Abbreviation:  Cell. Mol. Immunol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-06-07     Revised Date:  2014-08-19    
Medline Journal Info:
Nlm Unique ID:  101242872     Medline TA:  Cell Mol Immunol     Country:  China    
Other Details:
Languages:  eng     Pagination:  84-94     Citation Subset:  IM    
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MeSH Terms
Activating Transcription Factor 4 / genetics,  immunology*,  metabolism
Active Transport, Cell Nucleus / drug effects,  genetics,  immunology
Cell Nucleus / genetics,  immunology*,  metabolism
Cytokines / genetics,  immunology*,  secretion
Immunity, Innate / drug effects,  genetics
Lipopolysaccharides / pharmacology
Monocytes / immunology*,  metabolism
Proto-Oncogene Proteins c-jun / genetics,  immunology,  metabolism
Signal Transduction / drug effects,  genetics,  immunology*
Toll-Like Receptor 4 / genetics,  immunology*,  metabolism
U937 Cells
Reg. No./Substance:
0/ATF4 protein, human; 0/Cytokines; 0/Lipopolysaccharides; 0/Proto-Oncogene Proteins c-jun; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 145891-90-3/Activating Transcription Factor 4

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