RGD Reference Report - An oligodeoxynucleotide with AAAG repeats significantly attenuates burn-induced systemic inflammatory responses via inhibiting interferon regulatory factor 5 pathway.

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An oligodeoxynucleotide with AAAG repeats significantly attenuates burn-induced systemic inflammatory responses via inhibiting interferon regulatory factor 5 pathway.
Authors:	Xiao, Yue Lu, Wenting Li, Xin Zhao, Peiyan Yao, Yun Wang, Xiaohong Wang, Ying Lin, Zhipeng Yu, Yongli Hua, Shucheng Wang, Liying
Citation:	Xiao Y, etal., Mol Med. 2017 Sep;23:166-176. doi: 10.2119/molmed.2016.00243. Epub 2017 Jun 14.
RGD ID:	40907061
Pubmed:	PMID:28620671 (View Abstract at PubMed)
PMCID:	PMC5583065 (View Article at PubMed Central)
DOI:	DOI:10.2119/molmed.2016.00243 (Journal Full-text)
Previously, we showed that an oligodeoxynucleotide 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, the underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the AAAG ODN is consensus to interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether the AAAG ODN could attenuate burn injury induced systemic inflammatory responses via inhibiting IRF5 pathway. Using the mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the life span of the mice, decreased the expression of IRF5 at injured skin, reduced the production of TNF-α and IL-6 in blood and injured skin, and attenuated the ALI. Furthermore, AAAG ODN could bind IRF5 and inhibit the nuclear translocation of IRF5 in THP-1 cells. The data suggested that the 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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
IRF5	Human	Electric Burns	treatment	ISO	Irf5 (Mus musculus)		RGD
Irf5	Rat	Electric Burns	treatment	ISO	Irf5 (Mus musculus)		RGD
Irf5	Mouse	Electric Burns	treatment	IEP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Irf5 (interferon regulatory factor 5)

Genes (Mus musculus)

Irf5 (interferon regulatory factor 5)

Genes (Homo sapiens)

IRF5 (interferon regulatory factor 5)

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An oligodeoxynucleotide with AAAG repeats significantly attenuates burn-induced systemic inflammatory responses via inhibiting interferon regulatory factor 5 pathway.