Nrf2 and NF-κB/NLRP3 inflammasome pathways are involved in Prototheca bovis infections of mouse mammary gland tissue and mammary epithelial cells

Zhao, Wenpeng; Deng, Zhaoju; Barkema, Herman W.; Xu, Maolin; Gao, Jian; Liu, Gang; Lin, Yi; Kastelic, John P.; Han, Bo

doi:10.1016/j.freeradbiomed.2022.04.005

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…High IL-18 levels have also been reported in allergen-induced experimental and human EoE 37 , 47 . We have shown that both Aspergillus and corn extract challenge induce NLRP3 and caspase1 in esophageal epithelial cells and accumulated inflammatory macrophages in murine models of EoE these findings are consistent with the reports that indicates NLRP3 and caspase1 activation induces IL-18 48 , 49 . We provide evidence for a similar NLRP3- and caspase1-regulated IL-18 mechanistic pathway following allergen-induced EoE in mice.…”

Section: Discussionsupporting

confidence: 93%

Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis

Yadavalli,

Upparahalli Venkateshaiah,

Kumar

et al. 2023

Commun Biol

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The current report describes a stepwise mechanistic pathway of NLRP3/caspase1/IL-18-regulated immune responses operational in eosinophilic esophagitis (EoE). We show that esophageal epithelial cells and macrophage-derived NLRP3 regulated IL-18 initiate the disease and induced IL-5 facilitates eosinophil growth and survival. We also found that A. fumigatus-exposed IL-18−/− mice or IL-18-neutralized mice are protected from EoE induction. Most importantly, we present that intravascular rIL-18 delivery to ΔdblGATA mice and CD2-IL-5 mice show the development of EoE characteristics feature like degranulated and intraepithelial eosinophils, basal cell hyperplasia, remodeling and fibrosis. Similarly, we show an induced NLRP3-caspase1-regulated IL-18 pathway is also operational in human EoE. Lastly, we present the evidence that inhibitors of NLRP3 and caspase-1 (MCC950, BHB, and VX-765) protect A. fumigatus- and corn-extract-induced EoE pathogenesis. In conclusion, the current study provides a new understanding by implicating NLRP3/caspase1-regulated IL-18 pathway in EoE pathogenesis. The study has the clinical significance and novel therapeutic strategy, which depletes only IL-18-responsive pathogenic eosinophils, not naïve IL-5-generated eosinophils critical for maintaining innate immunity.

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Section: Discussionsupporting

confidence: 93%

Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis

Yadavalli,

Upparahalli Venkateshaiah,

Kumar

et al. 2023

Commun Biol

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“…AS-IV antagonized CDDP-induced oxidative stress by activating Nrf2 to up-regulate the proteins expression of NQO-1, GSTA1, and HO-1. Besides, Nrf2 is closely related to in ammatory response, which can negatively regulate NF-κB signaling [31]. Thus, we concluded that the activation of Nrf2 could endow AS-IV with anti-in ammatory activity to further enhance the effect of alleviating CDDPinduced nephrotoxicity.…”

Section: Discussionmentioning

confidence: 83%

Astragaloside IV alleviates cisplatin-induced nephrotoxicity in Lewis lung carcinoma mice and inhibits the epithelial-mesenchymal transition-mediated invasion and metastasis of lung cancer cells

Han

Chen

et al. 2022

Preprint

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Background: the high incidence of nephrotoxicity is a major limiting factor for the clinical use of cisplatin (CDDP), which affects severely the efficacy of chemotherapy. Astragaloside IV (AS-IV) is the characteristic monomer component of Astragalus membranaceus with prominent medical value in fibrosis, inflammation, autoimmune and cardiovascular diseases. However, whether AS-IV is feasible in combination with CDDP to alleviate the nephrotoxicity and the role of AS-IV in preventing the malignant transformation of tumor cells, have not been fully elucidated.Methods and results: this experiment established Lewis lung cancer mouse model through in vivo experiment. From the characteristics of mouse tumor and hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) analysis, kits, TUNEL and other experiments, it was proved that AS-IV could alleviate CDDP-induced nephrotoxicity through activating Nrf2 signaling to reduce the apoptosis of renal tubular epithelial cells and sensitize CDDP to enhance the inhibitory effect of Lewis lung carcinoma.In vitro, through Western blot, Wound healing assay and Transwell assays, we found that AS-IV could inhibit the invasion and metastasis ability of A549 cells via reversing the TNF-α and TGF-β co-stimulated epithelial-mesenchymal transition (EMT) process and down-regulated the expression of NF-κB(p65) synergistically. Conclusion: To sum up, the results of this study show that astragaloside IV reduces the nephrotoxicity of cisplatin induced Lewis lung cancer mice and inhibits the invasion and metastasis of lung cancer cells mediated by epithelial mesenchymal transformation.

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“…44,45 As a protective regulator, Nrf2 acts against activation of NLRP3 inflammasome by regulating the thioredoxin1/thioredoxin interacting protein complex, 46 and scavenging ROS. 47 Moreover, Nrf2 regulates ferroptosis via controlling the components of the glutathione and thioredoxin antioxidant systems at the transcriptional level, 48 and directly or indirectly regulating GPX4 expression and function. 49 Increasing Nrf2/GPX4 signalling enhances SOD levels, inhibits ferroptosis and proinflammatory cytokines levels.…”

Section: Discussionmentioning

confidence: 99%

“…Nrf2 activation directly blocks the transcription of the proinflammatory cytokines and inflammatory mediators, including tumour necrosis factor (TNF), IL‐1β, IL‐6 and COX‐2 44,45 . As a protective regulator, Nrf2 acts against activation of NLRP3 inflammasome by regulating the thioredoxin1/thioredoxin interacting protein complex, 46 and scavenging ROS 47 . Moreover, Nrf2 regulates ferroptosis via controlling the components of the glutathione and thioredoxin antioxidant systems at the transcriptional level, 48 and directly or indirectly regulating GPX4 expression and function 49 .…”

Section: Discussionmentioning

confidence: 99%

Anemoside B4 alleviates arthritis pain via suppressing ferroptosis‐mediated inflammation

Guo,

Yue,

Wang

et al. 2024

J Cellular Molecular Medi

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Chronic pain is the key manifestations of rheumatoid arthritis. Neuroinflammation in the spinal cord drives central sensitization and chronic pain. Ferroptosis has potentially important roles in the occurrence of neuroinflammation and chronic pain. In the current study, mouse model of collagen‐induced arthritis was established by intradermal injection of type II collagen in complete Freund's adjuvant (CFA) solution. CFA inducement resulted in swollen paw and ankle, mechanical and spontaneous pain, and impaired motor coordination. The spinal inflammation was triggered, astrocytes were activated, and increased NLRP3‐mediated inflammatory signal was found in CFA spinal cord. Oxidative stress and ferroptosis in the spinal cord were manifested. Meanwhile, enhancive spinal GSK‐3β activity and abnormal phosphorylated Drp1 were observed. To investigate the potential therapeutic options for arthritic pain, mice were intraperitoneally injected with AB4 for three consecutive days. AB4 treatment reduced pain sensitivity and increased the motor coordination. In the spinal cord, AB4 treatment inhibited NLRP3 inflammasome‐mediated inflammatory response, increased antioxidation, decreased mitochondrial reactive oxygen species and ferroptosis. Furthermore, AB4 decreased GSK‐3β activity by binding with GSK‐3β through five electrovalent bonds. Our findings indicated that AB treatment relieves arthritis pain by inhibiting GSK‐3β activation, increasing antioxidant capability, reducing Drp1‐mediated mitochondrial dysfunction and suppressing neuroinflammation.

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Nrf2 and NF-κB/NLRP3 inflammasome pathways are involved in Prototheca bovis infections of mouse mammary gland tissue and mammary epithelial cells

Cited by 11 publications

References 34 publications

Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis

Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis

Astragaloside IV alleviates cisplatin-induced nephrotoxicity in Lewis lung carcinoma mice and inhibits the epithelial-mesenchymal transition-mediated invasion and metastasis of lung cancer cells

Anemoside B4 alleviates arthritis pain via suppressing ferroptosis‐mediated inflammation

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