Short-chain Fatty Acids Abrogate Japanese Encephalitis Virus-induced Inflammation in Microglial Cells Via MiR-200a-3p/ZBTB20/IKβα Axis

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2024 Jun 13

PMID 38869276

Authors

Atreye Majumdar

Indira Priya Siva Venkatesh

Vivek Swarup

Anirban Basu

Affiliations

Soon will be listed here.

Abstract

Importance: The gut-brain axis plays a pivotal role in the physiological state of an organism. Gut microbiota-derived metabolites are known to play a role in brain disorders including neuroviral infections. Short-chain fatty acids (SCFAs) appear to quench inflammatory markers in Japanese encephalitis virus-infected microglial cells . Mechanistically, we demonstrate the interaction between miR-200a-3p and ZBTB20 in regulating the canonical nuclear factor kappa B (NF-κB) signaling pathway via transcriptional regulation of Iκβα. Findings of this study pave the way to a better understanding of SCFA mechanisms that can be used to develop strategies against viral neuroinflammation.

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References

Yadav P, Chakraborty P, Jha N, Dewanjee S, Jha A, Panda S . Molecular Mechanism and Role of Japanese Encephalitis Virus Infection in Central Nervous System-Mediated Diseases. Viruses. 2022; 14(12). PMC: 9781168. DOI: 10.3390/v14122686. View

Michell-Robinson M, Touil H, Healy L, Owen D, Durafourt B, Bar-Or A . Roles of microglia in brain development, tissue maintenance and repair. Brain. 2015; 138(Pt 5):1138-59. PMC: 5963417. DOI: 10.1093/brain/awv066. View

Berthois Y, Delfino C, Metellus P, Fina F, Nanni-Metellus I, Al Aswy H . Differential expression of miR200a-3p and miR21 in grade II-III and grade IV gliomas: evidence that miR200a-3p is regulated by O⁶-methylguanine methyltransferase and promotes temozolomide responsiveness. Cancer Biol Ther. 2014; 15(7):938-50. PMC: 4100995. DOI: 10.4161/cbt.28920. View

Stein R, Riber L . Epigenetic effects of short-chain fatty acids from the large intestine on host cells. Microlife. 2023; 4:uqad032. PMC: 10335734. DOI: 10.1093/femsml/uqad032. View

Chen S, Ye J, Chen X, Shi J, Wu W, Lin W . Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3. J Neuroinflammation. 2018; 15(1):150. PMC: 5960086. DOI: 10.1186/s12974-018-1193-6. View

Yu J, Chen J, Yang H, Chen S, Wang Z . Overexpression of miR‑200a‑3p promoted inflammation in sepsis‑induced brain injury through ROS‑induced NLRP3. Int J Mol Med. 2019; 44(5):1811-1823. PMC: 6777670. DOI: 10.3892/ijmm.2019.4326. View

Hu L, Zhang H, Wang B, Ao Q, He Z . MicroRNA-152 attenuates neuroinflammation in intracerebral hemorrhage by inhibiting thioredoxin interacting protein (TXNIP)-mediated NLRP3 inflammasome activation. Int Immunopharmacol. 2020; 80:106141. DOI: 10.1016/j.intimp.2019.106141. View

Bourassa M, Ratan R . The interplay between microRNAs and histone deacetylases in neurological diseases. Neurochem Int. 2014; 77:33-9. PMC: 4321688. DOI: 10.1016/j.neuint.2014.03.012. View

Li M, Van Esch B, Wagenaar G, Garssen J, Folkerts G, Henricks P . Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells. Eur J Pharmacol. 2018; 831:52-59. DOI: 10.1016/j.ejphar.2018.05.003. View

10.

Basu A, Dutta K . Recent advances in Japanese encephalitis. F1000Res. 2017; 6:259. PMC: 5357037. DOI: 10.12688/f1000research.9561.1. View

11.

Macfarlane L, Murphy P . MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics. 2011; 11(7):537-61. PMC: 3048316. DOI: 10.2174/138920210793175895. View

12.

Satheesan A, Sharma S, Basu A . Sodium Butyrate Induced Neural Stem/Progenitor Cell Death in an Experimental Model of Japanese Encephalitis. Metab Brain Dis. 2023; 38(8):2831-2847. DOI: 10.1007/s11011-023-01279-3. View

13.

Hazra B, Kumawat K, Basu A . The host microRNA miR-301a blocks the IRF1-mediated neuronal innate immune response to Japanese encephalitis virus infection. Sci Signal. 2017; 10(466):eaaf5185. DOI: 10.1126/scisignal.aaf5185. View

14.

Mukherjee S, Akbar I, Kumari B, Vrati S, Basu A, Banerjee A . Japanese Encephalitis Virus-induced let-7a/b interacted with the NOTCH-TLR7 pathway in microglia and facilitated neuronal death via caspase activation. J Neurochem. 2018; 149(4):518-534. DOI: 10.1111/jnc.14645. View

15.

Ma H, Yang L, Liu Y, Yan R, Wang R, Zhang P . Butyrate suppresses atherosclerotic inflammation by regulating macrophages and polarization via GPR43/HDAC-miRNAs axis in ApoE-/- mice. PLoS One. 2023; 18(3):e0282685. PMC: 9994734. DOI: 10.1371/journal.pone.0282685. View

16.

Caetano-Silva M, Rund L, Hutchinson N, Woods J, Steelman A, Johnson R . Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids. Sci Rep. 2023; 13(1):2819. PMC: 9935636. DOI: 10.1038/s41598-022-27086-x. View

17.

Ashraf U, Zhu B, Ye J, Wan S, Nie Y, Chen Z . MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11. J Virol. 2016; 90(9):4780-4795. PMC: 4836334. DOI: 10.1128/JVI.02586-15. View

18.

Vidal-Itriago A, Radford R, Aramideh J, Maurel C, Scherer N, Don E . Microglia morphophysiological diversity and its implications for the CNS. Front Immunol. 2022; 13:997786. PMC: 9627549. DOI: 10.3389/fimmu.2022.997786. View

19.

Turtle L, Solomon T . Japanese encephalitis - the prospects for new treatments. Nat Rev Neurol. 2018; 14(5):298-313. DOI: 10.1038/nrneurol.2018.30. View

20.

Sharma N, Kumawat K, Rastogi M, Basu A, Singh S . Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5. Sci Rep. 2016; 6:27685. PMC: 4901348. DOI: 10.1038/srep27685. View