J Appl Biomed 23:163-173, 2025 | DOI: 10.32725/jab.2025.018

Exosomes from LPS-stimulated macrophages alleviate neuroinflammatory responses by reducing pyroptosis in systemic lipopolysaccharide-induced mice

Tao Ying, Zhezhe Sun *
The First Affiliated Hospital of Ningbo University, Department of Neurology, Ningbo 315000, China

Central nervous system (CNS) inflammation occurs in cognitive dysfunction, but the underlying mechanisms remain unclear. The newly discovered pattern of cell death in recent years is called pyroptosis, which is distinguished from apoptosis and necrosis, and is mainly dependent on caspase-1 mediated inflammatory response. Stem-derived exosomes have immunomodulatory and immunosuppressive effects. In the present study, we aimed to investigate the exosomes (Ex) secreted by lipopolysaccharide (LPS)-stimulated macrophages (LPS-Ex) to attenuate the neuroinflammatory response caused by systemic LPS stimulation by attenuating pyroptosis. We studied lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6 mice by behavioral testing, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Western blotting, and other methods. We found that LPS-Ex can reduce the level of inflammatory factors, down-regulate the pyroptosis pathway and the inflammatory pathway of NF-κB, and improve the inflammatory response of neurological function in mice. The conclusion is that LPS-Ex relieves neuroinflammation by reducing pyroptosis. It can be used as a novel therapeutic strategy for neuroprotection and functional recovery in the onset of central nervous system inflammation.

Keywords: Exosomes; Lipopolysaccharide; Neuroinflammation; Pyroptosis
Grants and funding:

The study was supported by Ningbo Health Technology Project, No: 2020Y12 and 2022Y12.

Conflicts of interest:

The authors have no conflict of interest to declare.

Received: June 30, 2025; Revised: November 21, 2025; Accepted: December 5, 2025; Prepublished online: December 8, 2025; Published: December 17, 2025  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Ying T, Sun Z. Exosomes from LPS-stimulated macrophages alleviate neuroinflammatory responses by reducing pyroptosis in systemic lipopolysaccharide-induced mice. J Appl Biomed. 2025;23(4):163-173. doi: 10.32725/jab.2025.018. PubMed PMID: 41403229.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Catorce MN, Gevorkian G (2016). LPS-induced Murine Neuroinflammation Model: Main Features and Suitability for Pre-clinical Assessment of Nutraceuticals. Curr Neuropharmacol 14(2): 155-164. DOI: 10.2174/1570159x14666151204122017. Go to original source... Go to PubMed...
    2. Choi DS, Kim DK, Kim YK, Gho YS (2015). Proteomics of extracellular vesicles: Exosomes and ectosomes. Mass Spectrom Rev 34(4): 474-490. DOI: 10.1002/mas.21420. Go to original source... Go to PubMed...
    3. Courtois G, Gilmore TD (2006). Mutations in the NF-kappaB signaling pathway: implications for human disease. Oncogene 25(51): 6831-6843. DOI: 10.1038/sj.onc.1209939. Go to original source... Go to PubMed...
    4. Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ (2000). Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 19: 3365-3374. DOI: 10.1242/jcs.113.19.3365. Go to original source... Go to PubMed...
    5. DiPeso L, Ji DX, Vance RE, Price JV (2017). Cell death and cell lysis are separable events during pyroptosis. Cell Death Discov 3: 17070. DOI: 10.1038/cddiscovery.2017.70. Go to original source... Go to PubMed...
    6. García JA, Volt H, Venegas C, Doerrier C, Escames G, López LC, Acuña-Castroviejo D (2015). Disruption of the NF-kappaB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-alpha and blocks the septic response in mice. FASEB J 29(9): 3863-3875. DOI: 10.1096/fj.15-273656. Go to original source... Go to PubMed...
    7. He C, Xu Y, Sun J, Li L, Zhang JH, Wang Y (2023). Autophagy and Apoptosis in Acute Brain Injuries: From Mechanism to Treatment. Antioxid Redox Signal 38(1-3): 234-257. DOI: 10.1089/ars.2021.0094. Go to original source... Go to PubMed...
    8. He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, et al. (2015). Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell Res 25(12): 1285-1298. DOI: 10.1038/cr.2015.139. Go to original source... Go to PubMed...
    9. Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, et al. (2011). miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res 39(Database issue): D163-169. DOI: 10.1093/nar/gkq1107. Go to original source... Go to PubMed...
    10. Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, Chen J (2015). Microglial and macrophage polarization - new prospects for brain repair. Nat Rev Neurol 11(1): 56-64. DOI: 10.1038/nrneurol.2014.207. Go to original source... Go to PubMed...
    11. Ishrat T, Mohamed IN, Pillai B, Soliman S, Fouda AY, Ergul A, et al. (2015). Thioredoxin-interacting protein: a novel target for neuroprotection in experimental thromboembolic stroke in mice. Mol Neurobiol 51(2): 766-778. DOI: 10.1007/s12035-014-8766-x. Go to original source... Go to PubMed...
    12. Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K, Warming S, et al. (2015). Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526(7575): 666-671. DOI: 10.1038/nature15541. Go to original source... Go to PubMed...
    13. Lee MS, Hwang SK, Kim YE, Suh JK, Kim H, Lee SM, et al. (2019). Central nervous system vasculitis from Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children: A case report. Brain Dev 41(9): 820-825. DOI: 10.1016/j.braindev.2019.05.009. Go to original source... Go to PubMed...
    14. Lee SW, Gajavelli S, Spurlock MS, Andreoni C, de Rivero Vaccari JP, Bullock MR, et al. (2018). Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury. J Neurotrauma 35(14): 1681-1693. DOI: 10.1089/neu.2017.5530. Go to original source... Go to PubMed...
    15. Liu Z, Gan L, Xu Y, Luo D, Ren Q, Wu S, Sun C (2017). Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-kappaB/GSDMD signal in mice adipose tissue. J Pineal Res 63(1). DOI: 10.1111/jpi.12414. Go to original source... Go to PubMed...
    16. Ma B, Hottiger MO (2016). Crosstalk between Wnt/beta-Catenin and NF-kappaB Signaling Pathway during Inflammation. Front Immunol 7: 378. DOI: 10.3389/fimmu.2016.00378. Go to original source... Go to PubMed...
    17. Man SM, Karki R, Kanneganti TD (2017). Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev 277(1): 61-75. DOI: 10.1111/imr.12534. Go to original source... Go to PubMed...
    18. Ni H, Yang S, Siaw-Debrah F, Hu J, Wu K, He Z, et al. (2019). Exosomes Derived From Bone Mesenchymal Stem Cells Ameliorate Early Inflammatory Responses Following Traumatic Brain Injury. Front Neurosci 13: 14. DOI: 10.3389/fnins.2019.00014. Go to original source... Go to PubMed...
    19. Shi J, Gao W, Shao F (2017). Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem Sci 42(4): 245-254. DOI: 10.1016/j.tibs.2016.10.004. Go to original source... Go to PubMed...
    20. Sun Z, Nyanzu M, Yang S, Zhu X, Wang K, Ru J, et al. (2020). VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-κB Pathways to Improve Functional Outcomes in TBI Mice. Oxid Med Cell Longev 2020: 7879629. DOI: 10.1155/2020/7879629. Go to original source... Go to PubMed...
    21. Tavakoli Dargani Z, Singla DK (2019). Embryonic stem cell-derived exosomes inhibit doxorubicin-induced TLR4-NLRP3-mediated cell death-pyroptosis. Am J Physiol Heart Circ Physiol 317(2): H460-H471. DOI: 10.1152/ajpheart.00056.2019. Go to original source... Go to PubMed...
    22. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6): 654-659. DOI: 10.1038/ncb1596. Go to original source... Go to PubMed...
    23. Vezzani A, Granata T (2005). Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46(11): 1724-1743. DOI: 10.1111/j.1528-1167.2005.00298.x. Go to original source... Go to PubMed...
    24. Wang Y, Huang Y, Xu Y, Ruan W, Wang H, Zhang Y, et al. (2018). A Dual AMPK/Nrf2 Activator Reduces Brain Inflammation After Stroke by Enhancing Microglia M2 Polarization. Antioxid Redox Signal 28(2): 141-163. DOI: 10.1089/ars.2017.7003. Go to original source... Go to PubMed...
    25. Zhang X, Huang X, Hang D, Jin J, Li S, Zhu Y, Liu H (2024). Targeting pyroptosis with nanoparticles to alleviate neuroinflammatory for preventing secondary damage following traumatic brain injury. Sci Adv 10(2): eadj4260. DOI: 10.1126/sciadv.adj4260. Go to original source... Go to PubMed...
    26. Zheng Y, He E, Wang P, Shi Y, Zhao L, Liang J (2019). Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization. Biomater Sci 7(5): 2037-2049. DOI: 10.1039/C8BM01449C. Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content