AI Article Synopsis
- The cGAS-STING signaling pathway is a crucial part of the immune system, and its abnormal activation is linked to autoimmune diseases, highlighting the need for effective inhibitors.
- Glabridin (Glab), derived from licorice, was tested in lab models and mice to assess its impact on this pathway, showing significant inhibition of inflammatory responses.
- The study concludes that Glab could serve as a targeted treatment for autoimmune diseases linked to the cGAS-STING pathway by preventing the harmful activation of immune responses.
Article Abstract
Background: The cGAS-STING signaling pathway is an essential section of the natural immune system. In recent years, an increasing number of studies have shown a strong link between abnormal activation of the cGAS-STING signaling pathway, a natural immune pathway mediated by the nucleic acid receptor cGAS, and the development and progression of autoimmune diseases. Therefore, it is important to identify an effective compound to specifically downregulate this pathway for disease.
Methods: The effect of Glabridin (Glab) was investigated in BMDMs and Peripheral blood mononuclear cell (PBMC) by establishing an in vitro model of cGAS-STING signaling pathway activation. An activation model stimulated by DMXAA was also established in mice to study the effect of Glab. On the other hand, we investigated the possible mechanism of action of Glab and the effect of Glab on Trex1-deficient mice.
Results: In this research, we report that Glab, a major component of licorice, specifically inhibits the cGAS-STING signaling pathway by inhibiting the level of type I interferon and inflammatory cytokines (IL-6 and TNF-α). In addition, Glab has a therapeutic effect on innate immune diseases caused by abnormal cytoplasmic DNA in Trex1-deficient mice. Mechanistically, Glab can specifically inhibit the interaction of STING with IRF3.
Conclusion: Glab is a specific inhibitor of the cGAS-STING signaling pathway and may be used in the clinical therapy of cGAS-STING pathway-mediated autoimmune diseases.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10709943 | PMC |
| http://dx.doi.org/10.1186/s10020-023-00754-y | DOI Listing |
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