PMID- 25827060 OWN - NLM STAT- MEDLINE DCOM- 20150825 LR - 20161125 IS - 1742-4658 (Electronic) IS - 1742-464X (Linking) VI - 282 IP - 12 DP - 2015 Jun TI - Molecular mechanism of ER stress-induced gene expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in macrophages. PG - 2361-78 LID - 10.1111/febs.13284 [doi] AB - 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 RAW264.7 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 SP600125 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 (SOCS3). SOCS3 siRNA 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 RAW264.7 cells. In contrast, over-expression of SOCS3 reversed ERS-induced TRAIL expression. These findings provide in vitro evidence that SOCS3 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. CI - (c) 2015 FEBS. FAU - Huang, Yan AU - Huang Y AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Wang, Yarui AU - Wang Y AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Li, Xiaofeng AU - Li X AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Chen, Zhaolin AU - Chen Z AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Li, Xiaohui AU - Li X AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Wang, Huan AU - Wang H AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Ni, Mingming AU - Ni M AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. FAU - Li, Jun AU - Li J AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China. AD - Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150528 PL - England TA - FEBS J JT - The FEBS journal JID - 101229646 RN - 0 (Protein Kinase Inhibitors) RN - 0 (SOCS3 protein, human) RN - 0 (Socs3 protein, mouse) RN - 0 (Suppressor of Cytokine Signaling 3 Protein) RN - 0 (Suppressor of Cytokine Signaling Proteins) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFSF10 protein, human) RN - 0 (Tnfsf10 protein, mouse) RN - 0 (Transcription Factor AP-1) SB - IM MH - Animals MH - Cell Line, Transformed MH - Cell Line, Tumor MH - Cells, Cultured MH - *Endoplasmic Reticulum Stress/drug effects MH - *Gene Expression Regulation/drug effects MH - Humans MH - Immunologic Surveillance MH - MAP Kinase Signaling System/drug effects MH - Macrophages/cytology/drug effects/immunology/*metabolism MH - Macrophages, Peritoneal/cytology/drug effects/immunology/metabolism MH - Mice MH - Monocytes/drug effects/immunology/metabolism MH - Protein Kinase Inhibitors/pharmacology MH - RNA Interference MH - Suppressor of Cytokine Signaling 3 Protein MH - Suppressor of Cytokine Signaling Proteins/antagonists & inhibitors/genetics/*metabolism MH - TNF-Related Apoptosis-Inducing Ligand/agonists/antagonists & inhibitors/genetics/*metabolism MH - Transcription Factor AP-1/antagonists & inhibitors/metabolism OTO - NOTNLM OT - AP-1 OT - ER stress OT - SOCS3 OT - TRAIL OT - macrophages EDAT- 2015/04/02 06:00 MHDA- 2015/08/26 06:00 CRDT- 2015/04/02 06:00 PHST- 2014/10/12 00:00 [received] PHST- 2015/02/12 00:00 [revised] PHST- 2015/03/26 00:00 [accepted] PHST- 2015/04/02 06:00 [entrez] PHST- 2015/04/02 06:00 [pubmed] PHST- 2015/08/26 06:00 [medline] AID - 10.1111/febs.13284 [doi] PST - ppublish SO - FEBS J. 2015 Jun;282(12):2361-78. doi: 10.1111/febs.13284. Epub 2015 May 28.