Unknown

Dataset Information

0

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes.


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.

SUBMITTER: Zhang C 

PROVIDER: S-EPMC4003182 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes.

Zhang Chunyan C   Bai Nan N   Chang Antao A   Zhang Zhuhong Z   Yin Jing J   Shen Wenzhi W   Tian Yaping Y   Xiang Rong R   Liu Chenghu C  

Cellular & molecular immunology 20121217 1


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  ...[more]

Similar Datasets

| S-EPMC11020454 | biostudies-literature
| S-EPMC3494907 | biostudies-other
| S-EPMC4265613 | biostudies-literature
| S-EPMC5377761 | biostudies-literature
| S-EPMC3203086 | biostudies-literature
| S-EPMC8882599 | biostudies-literature
| S-EPMC7604537 | biostudies-literature
| S-EPMC6252340 | biostudies-literature
| S-EPMC4229102 | biostudies-literature
| S-EPMC8793151 | biostudies-literature