title: Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo.
abstract: Posttranscriptional regulation of IL-6 has been largely uncharacterized, with the exception of the ribonuclease Regnase-1, which prevents autoimmunity by destabilizing IL-6 mRNA. Here, we identified AT-rich interactive domain-containing protein 5A (Arid5a) as a unique RNA binding protein, which stabilizes IL-6 but not TNF-α mRNA through binding to the 3' untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1β, and IL-6. Arid5a deficiency inhibited elevation of IL-6 serum level in LPS-treated mice and suppressed IL-6 levels and the development of T(H)17 cells in experimental autoimmune encephalomyelitis. Importantly, Arid5a inhibited the destabilizing effect of Regnase-1 on IL-6 mRNA. These results indicate that Arid5a plays an important role in promotion of inflammatory processes and autoimmune diseases.
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Masuda
authors.forename: Barry
authors.initials: B
authors.lastname: Ripley
authors.forename: Riko
authors.initials: R
authors.lastname: Nishimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Mino
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008070:Lipopolysaccharides; D008156:Luciferases; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020871:RNA Stability / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C582683:Arid5a protein, mouse; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D008156:Luciferases; D012260:Ribonucleases; C541320:Zc3h12a protein, mouse
keywords: RNA-protein complex; immune regulation