An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

Molecular Medicine

Research Article

Yongli Yu¹  Zhipeng Lin²  Ying Wang²  Yun Yao²  Wenting Lu²  Peiyan Zhao²  Liying Wang²  Yue Xiao²  Xin Li²  Xiaohong Wang³  Shucheng Hua⁴ 

[1] Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun, China;Department of Molecular Biology, College of Basic Medical Sciences and Institute of Pediatrics, First Hospital, Norman Bethune Health Science Center, Jilin University, Changchun, China;Department of Respiratory Medicine, The First Hospital of Jilin University, Norman Bethune Health Science Center, Jilin University, Changchun, China;Department of Respiratory Medicine, The First Hospital of Jilin University, Norman Bethune Health Science Center, Jilin University, Changchun, China;Department of Molecular Biology or Department of Respiratory Medicine, College of Basic Medical Sciences and Institute of Pediatrics, First Hospital, or The First Hospital of Jilin University, Norman Bethune Health Science Center, Jilin University, Changchun, China;

关键词: ;   

DOI  :  10.2119/molmed.2016.00243

 received in 2016-12-03, accepted in 2017-06-06,  发布年份 2017

来源: Springer

【 摘 要 】

Previously, we showed that an oligodeoxynucleotide (ODN) with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, its underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the sequence of AAAG ODN is in consensus with the interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether AAAG ODN could attenuate burn injury-induced systemic inflammatory responses by inhibiting the IRF5 pathway. Using a mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the lifespan of the mice, decreased the expression of IRF5 in the injured skin, reduced the production of TNF-α and IL-6 in the blood and injured skin, and attenuated the ALI. These effects were correlated with AAAG ODN-mediated inhibition of nuclear translocation of IRF5. The data suggest that AAAG ODN could act as a cytoplasmic decoy capable of interfering the function of IRF5 and be developed as a drug candidate for the treatment of inflammatory diseases.

【 授权许可】

CC BY-NC-ND   
© The Author(s) 2017