Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

Autor:	Wang M; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Li XW; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Yuan SC; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Pan J; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Guo ZL; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Sun LM; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Jiang SZ; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China.; School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Zhao M; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Xue W; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Cai H; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Gu L; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Luo D; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China.; School of Medicine, Tsinghua University, Beijing 100084, China., Chen L; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China.; School of Medicine, Tsinghua University, Beijing 100084, China., Zhou XQ; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Han QY; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Li J; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Zhou T; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Xia T; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China., Li T; Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100850, China.; School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Jazyk:	angličtina
Zdroj:	Journal of molecular cell biology [J Mol Cell Biol] 2024 Sep 30; Vol. 16 (4).
DOI:	10.1093/jmcb/mjae015
Abstrakt:	The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity. (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)
Databáze:	MEDLINE
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