Open Access

MicroRNA‑451 relieves inflammation in cerebral ischemia‑reperfusion via the Toll‑like receptor 4/MyD88/NF‑κB signaling pathway

  • Authors:
    • Wenyan Li
    • Minghao Dong
    • Liangzhao Chu
    • Luqian Feng
    • Xiaochuan Sun
  • View Affiliations

  • Published online on: August 12, 2019     https://doi.org/10.3892/mmr.2019.10587
  • Pages: 3043-3054
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The present study was designed to investigate the role of microRNA‑451 (miRNA‑451) on cerebral ischemia‑reperfusion and to explore its possible mechanism. The expression of miRNA‑451 was downregulated in rats with cerebral ischemia‑reperfusion. In an in vitro model of cerebral ischemia‑reperfusion, the downregulation of miRNA‑451 increased inflammation, demonstrated by increased levels of tumor necrosis factor α, interleukin (IL)‑1b, IL‑6 and IL‑18. However, the upregulation of miRNA‑451 expression decreased inflammation in the same in vitro model of cerebral ischemia‑reperfusion. In addition, it was found that the downregulation of miRNA‑451 induced the expression of Toll‑like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor‑κB (NF‑κB)/p65. Moreover, the administration of a MyD88 inhibitor, ST 2825, reduced the expression of MyD88 and NF‑κB/p65 in the in vitro model of cerebral ischemia‑reperfusion, inhibiting the effects of miRNA‑451 upregulation on inflammation. A TLR4 inhibitor, TAK‑242, was used to reduce the expression of TLR4 in the in vitro model of cerebral ischemia‑reperfusion. TAK‑242 suppressed the effects of miRNA‑451 downregulation on inflammation. The present study suggested that miRNA‑451 regulated cerebral ischemia‑reperfusion‑induced inflammation, which is mediated through the TLR4/MyD88/NF‑κB signaling pathway.

References

1 

Dippel DW, Majoie CB, Roos YB, van der Lugt A, van Oostenbrugge RJ, van Zwam WH, Lingsma HF, Koudstaal PJ, Treurniet KM, van den Berg LA, et al: Influence of device choice on the effect of intra-arterial treatment for acute ischemic stroke in MR CLEAN (multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands). Stroke. 47:2574–2581. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Kim SK, Jang HM and Kim DY: The promoter polymorphism of NFKB1 gene contributes to susceptibility of ischemic stroke in Korean population. J Exerc Rehabil. 14:1096–1100. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Ceulemans AG, Zgavc T, Kooijman R, Hachimi-Idrissi S, Sarre S and Michotte Y: The dual role of the neuroinflammatory response after ischemic stroke: Modulatory effects of hypothermia. J Neuroinflammation. 7:742010. View Article : Google Scholar : PubMed/NCBI

4 

Candelario-Jalil E: Injury and repair mechanisms in ischemic stroke: Considerations for the development of novel neurotherapeutics. Curr Opin Investig Drugs. 10:644–654. 2009.PubMed/NCBI

5 

Kawakami S, Tahara Y, Noguchi T, Yagi N, Kataoka Y, Asaumi Y, Nakanishi M, Goto Y, Yokoyama H, Nonogi H, et al: Time to reperfusion in ST-segment elevation myocardial infarction patients with vs. without pre-hospital mobile telemedicine 12-lead electrocardiogram transmission. Circ J. 80:1624–1633. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Zhao GC, Yuan YL, Chai FR and Ji FJ: Effect of Melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia. Biomed Pharmacother. 89:1346–1352. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Zhou L, Zhang J, Wang C and Sun Q: Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model. Int J Immunopathol Pharmacol. 30:123–129. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Bonestroo HJ, Nijboer CH, van Velthoven CT, Kavelaars A, Hack CE, van Bel F and Heijnen CJ: Cerebral and hepatic inflammatory response after neonatal hypoxia-ischemia in newborn rats. Dev Neurosci. 35:197–211. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Naderi Y, Sabetkasaei M, Parvardeh S and Zanjani TM: Neuroprotective effect of minocycline on cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory and anti-oxidant properties in male rat. Brain Res Bull. 131:207–213. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Li X, Su L, Zhang X, Zhang C, Wang L, Li Y, Zhang Y, He T, Zhu X and Cui L: Ulinastatin downregulates TLR4 and NF-kB expression and protects mouse brains against ischemia/reperfusion injury. Neurol Res. 39:367–373. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Zhou J and Zhang J: Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction. Mol Med Rep. 10:971–976. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Liu X, Li F, Zhao S, Luo Y, Kang J, Zhao H, Yan F, Li S and Ji X: MicroRNA-124-mediated regulation of inhibitory member of apoptosis-stimulating protein of p53 family in experimental stroke. Stroke. 44:1973–1980. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Chen S, Wang M, Yang H, Mao L, He Q, Jin H, Ye ZM, Luo XY, Xia YP and Hu B: LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia. Biochem Biophys Res Commun. 485:167–173. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Truettner JS, Alonso OF, Bramlett HM and Dietrich WD: Therapeutic hypothermia alters microRNA responses to traumatic brain injury in rats. J Cereb Blood Flow Metab. 31:1897–1907. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Liu Q, Hu Y, Zhang M, Yan Y, Yu H and Ge L: microRNA-451 protects neurons against ischemia/reperfusion injury-induced cell death by targeting CELF2. Neuropsychiatr Dis Treat. 14:2773–2782. 2018. View Article : Google Scholar : PubMed/NCBI

16 

Leecharoenkiat K, Tanaka Y, Harada Y, Chaichompoo P, Sarakul O, Abe Y, Smith DR, Fucharoen S, Svasti S and Umemura T: Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease. Mol Med Rep. 15:2495–2502. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Hill MD, Demchuk AM, Goyal M, Jovin TG, Foster LD, Tomsick TA, von Kummer R, Yeatts SD, Palesch YY and Broderick JP; IMS3 Investigators, : Alberta Stroke Program early computed tomography score to select patients for endovascular treatment: Interventional Management of Stroke (IMS)-III Trial. Stroke. 45:444–449. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Zhu Z, Fu Y, Tian D, Sun N, Han W, Chang G, Dong Y, Xu X, Liu Q, Huang D and Shi FD: Combination of the immune modulator fingolimod with alteplase in acute ischemic stroke: A pilot trial. Circulation. 132:1104–1112. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Shan J, Sun L, Wang D and Li X: Comparison of the neuroprotective effects and recovery profiles of isoflurane, sevoflurane and desflurane as neurosurgical pre-conditioning on ischemia/reperfusion cerebral injury. Int J Clin Exp Pathol. 8:2001–2009. 2015.PubMed/NCBI

21 

Wang ZC, Lu H, Zhou Q, Yu SM, Mao YL, Zhang HJ, Zhang PC and Yan WJ: MiR-451 inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating p38MAPK signaling pathway. Int J Clin Exp Pathol. 8:14562–14567. 2015.PubMed/NCBI

22 

Zhang P, Guo ZF, Xu YM, Li YS and Song JG: N-Butylphthalide (NBP) ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway. Biomed Pharmacother. 83:658–666. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Zhou H, Yang WS, Li Y, Ren T, Peng L, Guo H, Liu JF, Zhou Y, Zhao Y, Yang LC and Jin X: Oleoylethanolamide attenuates apoptosis by inhibiting the TLR4/NF-κB and ERK1/2 signaling pathways in mice with acute ischemic stroke. Naunyn Schmiedebergs Arch Pharmacol. 390:77–84. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Sun X and Zhang H: miR-451 elevation relieves inflammatory pain by suppressing microglial activation-evoked inflammatory response via targeting TLR4. Cell Tissue Res. 374:487–495. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Ren Z, Zhang R, Li Y, Li Y, Yang Z and Yang H: Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo. Int J Mol Med. 40:1444–1456. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Liu R, Zhong X, Zeng J, Huang Z, Li X, Xiao H, Chen Q and Li D: 3′-Daidzein sulfonate sodium inhibits neuronal apoptosis induced by cerebral ischemia-reperfusion. Int J Mol Med. 39:1021–1028. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Kacimi R, Giffard RG and Yenari MA: Endotoxin-activated microglia injure brain derived endothelial cells via NF-κB, JAK-STAT and JNK stress kinase pathways. J Inflamm (Lond). 8:72011. View Article : Google Scholar : PubMed/NCBI

28 

Feola J, Barton A, Akbar A, Keillor J and Johnson GVW: Transglutaminase 2 modulation of NF-κB signaling in astrocytes is independent of its ability to mediate astrocytic viability in ischemic injury. Brain Res. 1668:1–11. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Sun Y, Peng R, Peng H, Liu H, Wen L, Wu T, Yi H, Li A and Zhang Z: miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic nephropathy. Mol Cell Endocrinol. 433:75–86. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Li, W., Dong, M., Chu, L., Feng, L., & Sun, X. (2019). MicroRNA‑451 relieves inflammation in cerebral ischemia‑reperfusion via the Toll‑like receptor 4/MyD88/NF‑κB signaling pathway. Molecular Medicine Reports, 20, 3043-3054. https://doi.org/10.3892/mmr.2019.10587
MLA
Li, W., Dong, M., Chu, L., Feng, L., Sun, X."MicroRNA‑451 relieves inflammation in cerebral ischemia‑reperfusion via the Toll‑like receptor 4/MyD88/NF‑κB signaling pathway". Molecular Medicine Reports 20.4 (2019): 3043-3054.
Chicago
Li, W., Dong, M., Chu, L., Feng, L., Sun, X."MicroRNA‑451 relieves inflammation in cerebral ischemia‑reperfusion via the Toll‑like receptor 4/MyD88/NF‑κB signaling pathway". Molecular Medicine Reports 20, no. 4 (2019): 3043-3054. https://doi.org/10.3892/mmr.2019.10587