Arid5a-deficient mice are highly resistant to bleomycin-induced lung injury

• Published in: International immunology 2017-02, Vol.29 (2), p.79-85
• Main Authors: Dubey, Praveen Kumar, Masuda, Kazuya, Nyati, Kishan Kumar, -Uz Zaman, Mohammad Mahabub, Chalise, Jaya Prakash, Millrine, David, Kai, Wang, Ripley, Barry, Kishimoto, Tadamitsu
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - immunology; Animals; Bleomycin - administration & dosage; DNA-Binding Proteins - genetics; Humans; Interleukin-6 - metabolism; Lung - pathology; Lung - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumonia - immunology; Pneumonia - therapy; Reactive Oxygen Species - metabolism; Respiratory Distress Syndrome, Adult - immunology; Respiratory Distress Syndrome, Adult - therapy; Transcription Factors - genetics
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxx004

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.