title: The Assembly of EDC4 and Dcp1a into Processing Bodies Is Critical for the Translational Regulation of IL-6.
abstract: Macrophages play critical roles in the onset of various diseases and in maintaining homeostasis. There are several functional subsets, of which M1 and M2 macrophages are of particular interest because they are differentially involved in inflammation and its resolution. Here, we investigated the differences in regulatory mechanisms between M1- and M2-polarized macrophages by examining mRNA metabolic machineries such as stress granules (SGs) and processing bodies (P-bodies). Human monocytic leukemia THP-1 cells cultured under M1-polarizing conditions (M1-THPs) had less ability to assemble oxidative-stress-induced SGs than those cultured under M2-polarizing conditions (M2-THPs). In contrast, P-body assembly in response to oxidative stress or TLR4 stimulation was increased in M1-THPs as compared to M2-THPs. These results suggest that mRNA metabolism is controlled differently in M1-THPs and M2-THPs. Interestingly, knocking down EDC4 or Dcp1a, which are components of P-bodies, severely reduced the production of IL-6, but not TNF-α in M1-THPs without decreasing the amount of IL-6 mRNA. This is the first report to demonstrate that the assembly of EDC4 and Dcp1a into P-bodies is critical in the posttranscriptional regulation of IL-6. Thus, improving our understanding of the mechanisms governing mRNA metabolism by examining macrophage subtypes may lead to new therapeutic targets.
authors.affiliation: Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Seto
authors.affiliation: Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida-Sugitani
authors.affiliation: Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Toyama-Sorimachi
mesh_terms: D002460:Cell Line; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000276:immunology*; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C507914:EDC4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D004722:Endoribonucleases; C466279:DCP1A protein, human