NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury

Nat Commun. 2017 Oct 16;8(1):950. doi: 10.1038/s41467-017-00930-9.

Zhikai Xiahou ¹ ², Xiangli Wang ¹ ², Juan Shen ¹ ², Xiaoxiao Zhu ³, Feng Xu ⁴, Rong Hu ⁵, Deyin Guo ⁶, Henan Li ⁷, Yong Tian ¹ ⁸, Yingfang Liu ⁹ ¹⁰, Huanhuan Liang ¹¹

Affiliations

1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
3 Laboratory Animal Center, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
4 Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
5 Center for Physical Examination, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
6 School of Medicine, Sun Yat-Sen University, Guangzhou, 510275, China.
7 Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China.
8 Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
9 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. liuyingfang@ibp.ac.cn.
10 School of Medicine, Sun Yat-Sen University, Guangzhou, 510275, China. liuyingfang@ibp.ac.cn.
11 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. hhliang@moon.ibp.ac.cn.

PMID: 29038465 DOI: 10.1038/s41467-017-00930-9

Abstract

Damage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat Infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. We show that extracellular NMI and IFP35 activate macrophages to release proinflammatory cytokines by activating nuclear factor-κB through the Toll-like Receptor 4 pathway. In addition, the serum levels of NMI are increased in patients who succumbed to severe inflammation. NMI deficiency reduces inflammatory responses and mortality in mouse models of sepsis and liver injury. We therefore propose that extracellular NMI and IFP35 exacerbate inflammation as DAMPs, making them potential therapeutic targets for clinical intervention.Damage-associated molecular patterns (DAMP) are important mediators of innate immunity. Here the authors show that N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs to promote inflammation by activating macrophages via the Toll-like Receptor 4 and NF-κB pathways.

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