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Molecular mechanism of ER stress‐induced gene expression of tumor necrosis factor‐related apoptosis‐inducing ligand ( TRAIL ) in macrophages
Author(s) -
Huang Yan,
Wang Yarui,
Li Xiaofeng,
Chen Zhaolin,
Li Xiaohui,
Wang Huan,
Ni Mingming,
Li Jun
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13284
Subject(s) - tumor necrosis factor alpha , microbiology and biotechnology , biology , apoptosis , signal transduction , cytokine , endoplasmic reticulum , transcription factor , gene expression , chemistry , immunology , gene , biochemistry
Tumor necrosis factor‐related apoptosis‐inducing ligand ( TRAIL ) is a member of the tumor necrosis factor superfamily, whose members are capable of inducing apoptosis and inflammation. Endoplasmic reticulum stress ( ERS ) plays a key role in immune surveillance in macrophages. TRAIL mRNA and protein expression have previously been detected in macrophages; however, whether ERS has any effects on TRAIL expression in macrophages has not yet been determined. Here, we demonstrate that thapsigargin ( TG ) and tunicamycin ( TM ), two ERS inducers activated macrophages were able to increase TRAIL mRNA and protein expression in RAW 264.7 macrophages, the culture supernatant of THP ‐1 cells, and mouse peritoneal macrophages, indicating that ERS as a potent inducer of TRAIL transcription and expression in macrophages. This effect was blocked by the specific JNK inhibitor SP 600125 and transcription factor AP ‐1 inhibitor SR 1130. Interestingly, at the molecular level, regulation of TRAIL expression by ERS was accompanied by a significant decrease in cytokine signaling suppressor 3 ( SOCS 3). SOCS 3 si RNA clearly increased the expression of TRAIL mRNA and protein under ERS by activating the AP ‐1 components phosphorylated c‐Jun and phosphorylated c‐Fos in RAW 264.7 cells. In contrast, over‐expression of SOCS 3 reversed ERS ‐induced TRAIL expression. These findings provide in vitro evidence that SOCS 3 plays a critical negative role in the regulation of ERS ‐induced TRAIL expression via the Jun N‐terminal kinase/ AP ‐1 signaling pathway in macrophages.