Baicalin Modulates Glycolysis via the PKC/Raf/MEK/ERK and PI3K/AKT Signaling Pathways to Attenuate IFN-I-Induced Neutrophil NETosis
Type I interferon (IFN-I), a pivotal component of the host’s innate antiviral immune system, can induce the formation of neutrophil extracellular traps (NETs) and facilitate inflammatory responses. Baicalin exhibits a range of pharmacological activities, including anti-inflammatory and immunomodulat...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/mi/8822728 |
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| Summary: | Type I interferon (IFN-I), a pivotal component of the host’s innate antiviral immune system, can induce the formation of neutrophil extracellular traps (NETs) and facilitate inflammatory responses. Baicalin exhibits a range of pharmacological activities, including anti-inflammatory and immunomodulatory effects. It has been reported that neutrophil glycolysis plays a pivotal role in the formation of NETs and the regulation of inflammatory response in immune modulation, regulated by IFN-I. However, it remains unclear whether baicalin regulates IFN-I-induced NETs formation through glycolysis. In this study, we induced the formation of NETs in vitro using IFN-I and observed that baicalin significantly reduced the formation of IFN-I-induced NETs. Furthermore, baicalin inhibited the production of pro-inflammatory cytokines, specifically interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), as well as the generation of reactive oxygen species (ROS) and chemotactic responses. Our findings further indicated that baicalin could inhibit both lactic acid and ATP levels in IFN-I-induced neutrophils, as well as the expression of glycolytic-related proteins, including HK2, HK3, PKM2, and LDHA. Moreover, following the administration of glycolytic agonists insulin, it was observed that heightened glycolytic activity significantly augmented NETs formation and the release of inflammatory cytokines, potentially regulated by PKC/Raf/MEK/ERK and PI3K/AKT signaling pathways. In conclusion, our findings indicated that baicalin may exert inhibitory effects on IFN-I-induced NETs formation and inflammatory cytokine production by modulating glycolysis, thereby providing further evidence for the potential clinical application of baicalin in the treatment of IFN-I-related inflammatory diseases. |
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| ISSN: | 1466-1861 |