Dimethyl itaconate inhibits LPS‑induced microglia inflammation and inflammasome‑mediated pyroptosis via inducing autophagy and regulating the Nrf‑2/HO‑1 signaling pathway

Yang, Shuxu; Zhang, Xingxing; Zhang, Hengli; Lin, Xiangxiang; Chen, Xijun; Zhang, Ying; Lin, Xiao Yan; Huang, Lijie; Zhuge, Qichuan

doi:10.3892/mmr.2021.12311

Cited by 22 publications

(13 citation statements)

References 58 publications

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“…Consistently, our data showed that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages. On the other hand, it has been reported that autophagy activation leads to the polarisation of macrophages ( Yang S. et al, 2021 ; Yang Y. et al, 2021 ). The present research indicates that autophagy induces the polarisation of M2 macrophages and that quercetin inhibits the autophagy in M2 macrophages.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990

Chen

Tang

et al. 2022

Front. Pharmacol.

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Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990

Chen

Tang

et al. 2022

Front. Pharmacol.

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“…By contrast, M2 macrophages are characterized by expressing high levels of IL-10 and Arg1 to relieve the inflammatory condition (Sica and Mantovani, 2012). A recent study found that DI promoted the transition from M1 to M2, reducing the expression of inflammatory mediators in microglia treated with LPS and ATP (Yang et al, 2021). In our study, DI promoted Arg1 and CD206 and inhibited the expression of iNOS and CD86 in CFA-treated paw tissues.…”

Section: Discussionsupporting

confidence: 52%

Dimethyl Itaconate Attenuates CFA-Induced Inflammatory Pain via the NLRP3/ IL-1β Signaling Pathway

et al. 2022

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Itaconate plays a prominent role in anti-inflammatory effects and has gradually been ushered as a promising drug candidate for treating inflammatory diseases. However, its significance and underlying mechanism for inflammatory pain remain unexplored. In the current study, we investigated the effects and mechanisms of Dimethyl Itaconate (DI, a derivative of itaconate) on Complete Freund’s adjuvant (CFA)-induced inflammatory pain in a rodent model. Here, we demonstrated that DI significantly reduced mechanical allodynia and thermal hyperalgesia. The DI-attenuated neuroinflammation was evident with the amelioration of infiltrative macrophages in peripheral sites of the hind paw and the dorsal root ganglion. Concurrently, DI hindered the central microglia activation in the spinal cord. Mechanistically, DI inhibited the expression of pro-inflammatory factors interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α) and upregulated anti-inflammatory factor IL-10. The analgesic mechanism of DI was related to the downregulation of the nod-like receptor protein 3 (NLRP3) inflammasome complex and IL-1β secretion. This study suggested possible novel evidence for prospective itaconate utilization in the management of inflammatory pain.

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“…Itaconate derivatives, when cultured with microglia stimulated with LPS + ATP, inhibit the NLRP3 inflammasome and IL-1β release. (Yang et al, 2021).…”

Section: Idh2mentioning

confidence: 99%

Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

Strogulski,

Portela,

Polster

et al. 2023

Journal of Neurochemistry

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Traumatic brain injury (TBI) is a devastating neurological disorder caused by a physical impact to the brain that promotes diffuse damage and chronic neurodegeneration. Key mechanisms believed to support secondary brain injury include mitochondrial dysfunction and chronic neuroinflammation. Microglia and brain‐infiltrating macrophages are responsible for neuroinflammatory cytokine and reactive oxygen species (ROS) production after TBI. Their production is associated with loss of homeostatic microglial functions such as immunosurveillance, phagocytosis, and immune resolution. Beyond providing energy support, mitochondrial metabolic pathways reprogram the pro‐ and anti‐inflammatory machinery in immune cells, providing a critical immunometabolic axis capable of regulating immunologic response to noxious stimuli. In the brain, the capacity to adapt to different environmental stimuli derives, in part, from microglia's ability to recognize and respond to changes in extracellular and intracellular metabolite levels. This capacity is met by an equally plastic metabolism, capable of altering immune function. Microglial pro‐inflammatory activation is associated with decreased mitochondrial respiration, whereas anti‐inflammatory microglial polarization is supported by increased oxidative metabolism. These metabolic adaptations contribute to neuroimmune responses, placing mitochondria as a central regulator of post‐traumatic neuroinflammation. Although it is established that profound neurometabolic changes occur following TBI, key questions related to metabolic shifts in microglia remain unresolved. These include (a) the nature of microglial mitochondrial dysfunction after TBI, (b) the hierarchical positions of different metabolic pathways such as glycolysis, pentose phosphate pathway, glutaminolysis, and lipid oxidation during secondary injury and recovery, and (c) how immunometabolism alters microglial phenotypes, culminating in chronic non‐resolving neuroinflammation. In this basic neurochemistry review article, we describe the contributions of immunometabolism to TBI, detail primary evidence of mitochondrial dysfunction and metabolic impairments in microglia and macrophages, discuss how major metabolic pathways contribute to post‐traumatic neuroinflammation, and set out future directions toward advancing immunometabolic phenotyping in TBI.image

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Dimethyl itaconate inhibits LPS‑induced microglia inflammation and inflammasome‑mediated pyroptosis via inducing autophagy and regulating the Nrf‑2/HO‑1 signaling pathway

Cited by 22 publications

References 58 publications

RETRACTED: Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990

RETRACTED: Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990

Dimethyl Itaconate Attenuates CFA-Induced Inflammatory Pain via the NLRP3/ IL-1β Signaling Pathway

Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

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