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An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-Induced Systemic Inflammatory Responses by Inhibiting Interferon Regulatory Factor 5 Pathway

Authors
Yue Xiao, Wenting Lu, Xin Li, Peiyan Zhao, Yun Yao, Xiaohong Wang, Ying Wang, Zhipeng Lin, Yongli Yu, Shucheng Hua, and Liying Wang
Abstract
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.
Volume
2017
Page Range
166-176
DOI
10.2119/molmed.2016.00243
Date Published
June 14, 2017
Article PDF
16_243_Xiao.pdf2979 KB
Supplemental Data
16_243_Xiao_Suppl.pdf423 KB
Keywords
Xiao, Lu, Li, Zhao, Yao, Wang, Lin, Yu, Hua, oligodeoxynucleotide, ODN, AAAG, systemic inflammatory response, tissue damage, burn injury, TLR signaling pathway, interferon regulatory factor, IRF5
Article Type
Research Article