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Biochemical pharmacology

Biochemical pharmacology

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Midazolam negatively regulates STING trafficking and activation and protects against Listeria monocytogenes infection in vivo

Published:4 July 2025 DOI: 10.1016/j.bcp.2025.117096 PMID: 40619030
Xiuling Lin , Liang Ma , Jingjing Huang , Yijing Cai , Xinpei Gu , Yao Chen , Fengxian Li , Pingzheng Zhou

Abstract

The stimulator of interferon genes (STING) plays a critical role in innate immunity, where precise regulation of its activity is essential for pathogen clearance and avoiding harmful immune responses. The development of STING inhibitors has been proposed to alleviate a variety of autoimmune and inflammatory diseases. In this study, using cell line models, we demonstrate that midazolam, a commonly used anesthetic, inhibited STING signaling in macrophages and epithelial-derived cell lines. Specifically, midazolam or translocator protein (TSPO) silencing impaired STING trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus in a proteasome-dependent manner. Furthermore, midazolam effectively suppressed STING over-activation and type I interferons (IFNs) signaling activation induced by STING mutations or excessive DNA accumulation in three-prime repair exonuclease 1 knockout (Trex1-/-) mouse embryonic fibroblasts. Of note, midazolam reduced type I IFNs expression and protected mice against Listeria monocytogenes-induced infection in vivo. These findings suggest that midazolam or TSPO inhibitors could be a promising therapeutic agent for modulating STING activation and treating related inflammatory diseases.

Substances (10)

Materials
Procduct Name CAS Molecular Formula Supplier Price
3-METHYLADENINE 5142-23-4 C6H7N5 396 suppliers $12.00-$4500.00
3-METHYLADENINE 5142-23-4 C6H7N5 396 suppliers $12.00-$4500.00
3-METHYLADENINE 5142-23-4 C6H7N5 396 suppliers $12.00-$4500.00
3-METHYLADENINE 5142-23-4 C6H7N5 396 suppliers $12.00-$4500.00
Vadimezan 117570-53-3 C17H14O4 258 suppliers $9.00-$20100.00
Vadimezan 117570-53-3 C17H14O4 258 suppliers $9.00-$20100.00
Vadimezan 117570-53-3 C17H14O4 258 suppliers $9.00-$20100.00
Vadimezan 117570-53-3 C17H14O4 258 suppliers $9.00-$20100.00
3H-?Purin-?6-?amine, 3-?methyl- 5142-23-4 C6H7N5 - Inquiry
3H-?Purin-?6-?amine, 3-?methyl- 5142-23-4 C6H7N5 - Inquiry
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