title: Arid5a-deficient mice are highly resistant to bleomycin-induced lung injury.
abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are among the major causes of death worldwide due to acute inflammation in the lung. AT-rich interactive domain-containing 5a (Arid5a) is an RNA-binding protein involved in inflammatory autoimmune disease through post-transcriptional control of Il6, Stat3 and Tbx21 gene expression. We found that Arid5a-deficient mice were highly refractory to bleomycin (BLM)-induced lethality. Arid5a deficiency suppressed lung pathology, cytokine production (especially, IL-6), and clinical symptoms in BLM-treated mice. Production of reactive oxygen species (ROS) in response to BLM-induced cellular damage was inhibited in Arid5a-deficient mice, potentially affecting the level of oxidized 1-palmitoyl-2-arachidonoyl-phosphaticylcholine (OxPAPC) production. OxPAPC, which is supposed to be a TLR4/TLR2 ligand, stimulated expression of the Arid5a and Il6 genes. Thus, reduction of ROS production in Arid5a-deficient mice could mitigate OxPAPC production, which in turn decreases IL-6 production in vivo due to dysregulated post-transcriptional regulation by loss of Arid5a. Therefore, the control of Arid5a expression represents a potential therapeutic target for treatment of ALI and ARDS.
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Dubey
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Kishan Kumar
authors.initials: KK
authors.lastname: Nyati
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Mohammad Mahabub
authors.initials: MM
authors.lastname: -Uz Zaman
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Jaya Prakash
authors.initials: JP
authors.lastname: Chalise
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: David
authors.initials: D
authors.lastname: Millrine
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Wang
authors.initials: W
authors.lastname: Kai
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Barry
authors.initials: B
authors.lastname: Ripley
authors.affiliation: Laboratory of Immune Regulation, World Premier International-Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan.
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C582683:Arid5a protein, mouse; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D001761:Bleomycin
keywords: IL-6; OxPAPC; ROS; acute lung injury; acute respiratory distress syndrome