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Int Immunopharmacol. 2017 Nov;52:245-252. doi: 10.1016/j.intimp.2017.09.010. Epub 2017 Sep 25.

4(3H)-Quinazolone regulates innate immune signaling upon respiratory syncytial virus infection by moderately inhibiting the RIG-1 pathway in RAW264.7 cell.

Author information

1
Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou 225312, China; Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: hlw9752@163.com.
2
Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou 225312, China.
3
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
4
Department of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China.
5
Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou 225312, China. Electronic address: zyykjc@sina.com.

Abstract

The root of Isatis indigotica, also known as Ban-Lan-Gen (BLG), is commonly used for prevention and early treatment of respiratory virus infection, but the underlying mechanisms of action remain unclear. In the early stage of infection, the innate immune system is activated by virus, and related immune cells such as macrophages secrete large amounts of cytokines including IFNs and ILs. On the one hand, these cytokines can remove virus. On the other hand, they dominantly mediate the inflammatory injury caused by viral infection. This study evaluated the effects of the main active plasma components of BLG (tryptanthrin B, 4(3H)-Quinazolone and epigoitrin) on the innate immune response of respiratory syncytial virus (RSV)-activated mouse macrophages. ELISA, real-time PCR and reporter gene assay all showed that 4(3H)-Quinazolone inhibited RSV-induced IFN-β secretion in mouse macrophages in a dose-dependent manner within a concentration range (0.3125-1.25μM) having no effects on cell viability, but the inhibitory effects were inferior to those of ribavirin. Western blot analyses further revealed that 4(3H)-Quinazolone inhibited RSV-induced expression of RIG-I (Retinoic acid-Inducible Gene-I) in mouse macrophages dose-dependently, thereby suppressing the transcription of IFN-β, with lower effects than those of ribavirin. This may be one of the important mechanisms by which BLG inhibited inflammatory injury without affecting the immune system to eliminate virus. The results inspire future studies to elucidate the antiviral mechanisms of traditional Chinese medicine drugs.

KEYWORDS:

4(3H)-Quinazolone; Innate immune signal; RIG-I; Respiratory syncytial virus

PMID:
28957692
DOI:
10.1016/j.intimp.2017.09.010
[Indexed for MEDLINE]

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