Arid5a-deficient mice are highly resistant to bleomycin-induced lung injury
| Autor: | Barry Ripley, David Millrine, Jaya Prakash Chalise, Kazuya Masuda, Kishan K. Nyati, Mohammad Mahabub-Uz Zaman, Wang Kai, Tadamitsu Kishimoto, Praveen K Dubey |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine ARDS medicine.medical_treatment Acute Lung Injury Immunology Inflammation Lung injury Bleomycin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Immunology and Allergy STAT3 Interleukin 6 Lung Mice Knockout Respiratory Distress Syndrome biology Interleukin-6 business.industry Pneumonia General Medicine medicine.disease DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology Cytokine 030228 respiratory system chemistry Cancer research biology.protein TLR4 medicine.symptom Reactive Oxygen Species business Transcription Factors |
| Zdroj: | International Immunology. 29:79-85 |
| ISSN: | 1460-2377 0953-8178 |
| DOI: | 10.1093/intimm/dxx004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|