ATF4 is Directly Recruited by TLR4 Signaling and Positively Regulates TLR4-trigged Cytokine Production in Human Monocytes

Overview

Journal Cell Mol Immunol

Date 2012 Dec 18

PMID 23241898

Citations 56

Authors

Chunyan Zhang

Nan Bai

Antao Chang

Zhuhong Zhang

Jing Yin

Wenzhi Shen

Yaping Tian

Rong Xiang

Chenghu Liu

Affiliations

Soon will be listed here.

Abstract

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.

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