Necrostatin‑1 ameliorates the pathogenesis of experimental autoimmune encephalomyelitis by suppressing apoptosis and necroptosis of oligodendrocyte precursor cells

Wang,Ying; Guo,Li; Wang,Jueqiong; Shi,Wei; Xia,Zhilun; Li,Bin

doi:10.3892/etm.2019.8005

Necrostatin‑1 ameliorates the pathogenesis of experimental autoimmune encephalomyelitis by suppressing apoptosis and necroptosis of oligodendrocyte precursor cells

Authors:
- Ying Wang
- Li Guo
- Jueqiong Wang
- Wei Shi
- Zhilun Xia
- Bin Li
View Affiliations

Affiliations: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: September 13, 2019 https://doi.org/10.3892/etm.2019.8005
Pages: 4113-4119

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

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

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuronal demyelination. MS pathogenesis occurs via multiple mechanisms, and is mediated in part by oligodendrocyte apoptosis and a robust inflammatory response. In the present study, Necrostatin‑1 (Nec‑1), a specific inhibitor of the receptor‑interacting protein 1 kinase domain, was revealed to effectively alleviate the severity and pathological damage associated with experimental autoimmune encephalomyelitis (EAE), a commonly used mouse model of MS. In addition, treatment with Nec‑1 significantly decreased the number of lesions and inflammatory cell infiltrates in spinal cord tissues, as well as the production of associated pro‑inflammatory cytokines, including tumor necrosis factor α (TNFα), interferon‑γ and interleukin‑1β. Nec‑1 also suppressed TNFα + zVAD‑fmk‑induced apoptosis and necroptosis in primary oligodendrocyte precursor cells. The present study revealed that Nec‑1 effectively attenuated the progression of EAE by suppressing apoptosis and necroptosis in oligodendrocytes, and represents a potential novel therapeutic agent for the treatment of MS.

View Figures

View References

1	Sedal L, Winkel A, Laing J, Law LY and McDonald E: Current concepts in multiple sclerosis therapy. Degener Neurol Neuromuscul Dis. 7:109–125. 2017.PubMed/NCBI
2	Lemus HN, Warrington AE and Rodriguez M: Multiple Sclerosis: Mechanisms of disease and strategies for myelin and axonal repair. Neurol Clin. 36:1–11. 2018. View Article : Google Scholar : PubMed/NCBI
3	Kacperska MJ, Walenczak J and Tomasik B: Plasmatic microRNA as potential biomarkers of multiple sclerosis: Literature review. Adv Clin Exp Med. 25:775–779. 2016. View Article : Google Scholar : PubMed/NCBI
4	Simon M, Ipek R, Homola GA, Rovituso DM, Schampel A, Kleinschnitz C and Kuerten S: Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous system in a mouse model of multiple sclerosis. J Neuroinflammation. 15:2252018. View Article : Google Scholar : PubMed/NCBI
5	Linkermann A, Hackl MJ, Kunzendorf U, Walczak H, Krautwald S and Jevnikar AM: Necroptosis in immunity and ischemia-reperfusion injury. Am J Transplant. 13:2797–2804. 2013. View Article : Google Scholar : PubMed/NCBI
6	Yang R, Hu K, Chen J, Zhu S, Li L, Lu H, Li P and Dong R: Necrostatin-1 protects hippocampal neurons against ischemia/reperfusion injury via the RIP3/DAXX signaling pathway in rats. Neurosci Lett. 651:207–215. 2017. View Article : Google Scholar : PubMed/NCBI
7	Tristao VR, Goncalves PF, Dalboni MA, Batista MC, Durao Mde S Jr and Monte JC: Nec-1 protects against nonapoptotic cell death in cisplatin-induced kidney injury. Ren Fail. 34:373–377. 2012. View Article : Google Scholar : PubMed/NCBI
8	Koudstaal S, Oerlemans MI, Van der Spoel TI, Janssen AW, Hoefer IE, Doevendans PA, Sluijter JP and Chamuleau SA: Necrostatin-1 alleviates reperfusion injury following acute myocardial infarction in pigs. Eur J Clin Invest. 45:150–159. 2015. View Article : Google Scholar : PubMed/NCBI
9	Dionisio PE, Oliveira SR, Amaral JS and Rodrigues CM: Loss of microglial parkin inhibits necroptosis and contributes to neuroinflammation. Mol Neurobiol. 56:2990–3004. 2019. View Article : Google Scholar : PubMed/NCBI
10	Liu ZY, Wu B, Guo YS, Zhou YH, Fu ZG, Xu BQ, Li JH, Jing L, Jiang JL, Tang J and Chen ZN: Necrostatin-1 reduces intestinal inflammation and colitis-associated tumorigenesis in mice. Am J Cancer Res. 5:3174–3185. 2015.PubMed/NCBI
11	Han W, Xie J, Fang Y, Wang Z and Pan H: Nec-1 enhances shikonin-induced apoptosis in leukemia cells by inhibition of RIP-1 and ERK1/2. Int J Mol Sci. 13:7212–7225. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zhe-Wei S, Li-Sha G and Yue-Chun L: The role of necroptosis in cardiovascular disease. Front Pharmacol. 9:7212018. View Article : Google Scholar : PubMed/NCBI
13	Shan B, Pan H, Najafov A and Yuan J: Necroptosis in development and diseases. Genes Dev. 32:327–340. 2018. View Article : Google Scholar : PubMed/NCBI
14	Dhuriya YK and Sharma D: Necroptosis: A regulated inflammatory mode of cell death. J Neuroinflammation. 15:1992018. View Article : Google Scholar : PubMed/NCBI
15	Linkermann A, Hackl MJ, Kunzendorf U, Walczak H, Krautwald S and Jevnikar AM: Necroptosis in immunity and ischemia-reperfusion injury. Am J Transplant. 13:2797–2804. 2013. View Article : Google Scholar : PubMed/NCBI
16	Wu W, Liu P and Li J: Necroptosis: An emerging form of programmed cell death. Crit Rev Oncol Hematol. 82:249–258. 2012. View Article : Google Scholar : PubMed/NCBI
17	Dhib-Jalbut S and Kalvakolanu DV: Microglia and necroptosis: The culprits of neuronal cell death in multiple sclerosis. Cytokine. 76:583–584. 2015. View Article : Google Scholar : PubMed/NCBI
18	Ofengeim D, Ito Y, Najafov A, Zhang Y, Shan B, DeWitt JP, Ye J, Zhang X, Chang A, Vakifahmetoglu-Norberg H, et al: Activation of necroptosis in multiple sclerosis. Cell Rep. 10:1836–1849. 2015. View Article : Google Scholar : PubMed/NCBI
19	Lu C, Chen X, Wang Q, Xu X and Xu B: TNFα promotes glioblastoma A172 cell mitochondrial apoptosis via augmenting mitochondrial fission and repression of MAPK-ERK-YAP signaling pathways. Onco Targets Ther. 11:7213–7227. 2018. View Article : Google Scholar : PubMed/NCBI
20	Shioda M, Muneta T, Tsuji K, Mizuno M, Komori K, Koga H and Sekiya I: TNFα promotes proliferation of human synovial MSCs while maintaining chondrogenic potential. PLoS One. 12:e01777712017. View Article : Google Scholar : PubMed/NCBI
21	Bryan C, Sammour I, Guerra K, Sharma M, Dapaah-Siakwan F, Huang J, Zambrano R, Benny M, Wu S and Young K: TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia. Pediatr Res. 85:390–397. 2019. View Article : Google Scholar : PubMed/NCBI
22	Lee E, Ouzounova M, Piranlioglu R, Ma MT, Guzel M, Marasco D, Chadli A, Gestwicki JE, Cowell JK, Wicha MS, et al: The pleiotropic effects of TNFα in breast cancer subtypes is regulated by TNFAIP3/A20. Oncogene. 38:469–482. 2019. View Article : Google Scholar : PubMed/NCBI
23	Pegoretti V, Baron W, Laman JD and Eisel ULM: Selective modulation of TNF-TNFRs signaling: Insights for multiple sclerosis treatment. Front Immunol. 9:9252018. View Article : Google Scholar : PubMed/NCBI
24	Zhou Y, Taylor B, van der Mei I, Stewart N, Charlesworth J, Blizzard L, Ponsonby AL, Dwyer T, Pittas F and Simpson S Jr: Genetic variation in PBMC-produced IFN-γ and TNF-α associations with relapse in multiple sclerosis. J Neurol Sci. 349:40–44. 2015. View Article : Google Scholar : PubMed/NCBI
25	Dendrou CA, Bell JI and Fugger L: A clinical conundrum: The detrimental effect of TNF antagonists in multiple sclerosis. Pharmacogenomics. 14:1397–1404. 2013. View Article : Google Scholar : PubMed/NCBI
26	Haji N, Mandolesi G, Gentile A, Sacchetti L, Fresegna D, Rossi S, Musella A, Sepman H, Motta C, Studer V, et al: TNF-α-mediated anxiety in a mouse model of multiple sclerosis. Exp Neurol. 237:296–303. 2012. View Article : Google Scholar : PubMed/NCBI
27	Jurewicz AM, Walczak AK and Selmaj KW: Shedding of TNF receptors in multiple sclerosis patients. Neurology. 53:1409–1414. 1999. View Article : Google Scholar : PubMed/NCBI
28	Kamali-Sarvestani E, Nikseresht A, Aflaki E, Sarvari J and Gharesi-Fard B: TNF-alpha, TNF-beta and IL-4 gene polymorphisms in Iranian patients with multiple sclerosis. Acta Neurol Scand. 115:161–166. 2007. View Article : Google Scholar : PubMed/NCBI
29	Wang Y, Bi Y, Xia Z, Shi W, Li B, Li B, Chen L and Guo L: Butylphthalide ameliorates experimental autoimmune encephalomyelitis by suppressing PGAM5-induced necroptosis and inflammation in microglia. Biochem Biophys Res Commun. 497:80–86. 2018. View Article : Google Scholar : PubMed/NCBI
30	Alwahaibi NY, Alkhatri AS and Kumar JS: Hematoxylin and eosin stain shows a high sensitivity but sub-optimal specificity in demonstrating iron pigment in liver biopsies. Int J Appl Basic Med Res. 5:169–171. 2015. View Article : Google Scholar : PubMed/NCBI
31	Chen Y, Balasubramaniyan V, Peng J, Hurlock EC, Tallquist M, Li J and Lu QR: Isolation and culture of rat and mouse oligodendrocyte precursor cells. Nat Protoc. 2:1044–1051. 2007. View Article : Google Scholar : PubMed/NCBI
32	Tao F, Tian X, Lu M and Zhang Z: A novel lncRNA, Lnc-OC1, promotes ovarian cancer cell proliferation and migration by sponging miR-34a and miR-34c. J Genet Genomics. 45:137–145. 2018. View Article : Google Scholar : PubMed/NCBI
33	Zhang Z, Zhang B, Li W, Fu L, Fu L, Zhu Z and Dong JT: Epigenetic silencing of miR-203 upregulates SNAI2 and contributes to the invasiveness of malignant breast cancer cells. Genes Cancer. 2:782–791. 2011. View Article : Google Scholar : PubMed/NCBI
34	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
35	Lenhausen AM, Wilkinson AS, Lewis EM, Dailey KM, Scott AJ, Khan S and Wilkinson JC: Apoptosis inducing factor binding protein PGAM5 triggers mitophagic cell death that is inhibited by the ubiquitin ligase activity of X-linked inhibitor of apoptosis. Biochemistry. 55:3285–3302. 2016. View Article : Google Scholar : PubMed/NCBI
36	Liao L, Shang L, Li N, Wang S, Wang M, Huang Y, Chen D, Huang J and Xiong K: Mixed lineage kinase domain-like protein induces RGC-5 necroptosis following elevated hydrostatic pressure. Acta Biochim Biophys Sin (Shanghai). 49:879–889. 2017. View Article : Google Scholar : PubMed/NCBI
37	Cudrici C, Niculescu T, Niculescu F, Shin ML and Rus H: Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement. J Rehabil Res Dev. 43:123–132. 2006. View Article : Google Scholar : PubMed/NCBI
38	Van Kaer L, Postoak JL, Wang C, Yang G and Wu L: Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE. Cell Mol Immunol. 16:531–539. 2019. View Article : Google Scholar : PubMed/NCBI
39	Robinson AP, Harp CT, Noronha A and Miller SD: The experimental autoimmune encephalomyelitis (EAE) model of MS: Utility for understanding disease pathophysiology and treatment. Handb Clin Neurol. 122:173–189. 2014. View Article : Google Scholar : PubMed/NCBI
40	Yuan J, Amin P and Ofengeim D: Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat Rev Neurosci. 20:19–33. 2019. View Article : Google Scholar : PubMed/NCBI
41	Shao L, Yu S, Ji W, Li H and Gao Y: The Contribution of Necroptosis in Neurodegenerative Diseases. Neurochem Res. 42:2117–2126. 2017. View Article : Google Scholar : PubMed/NCBI
42	Zhang S, Wang Y, Li D, Wu J, Si W and Wu Y: Necrostatin-1 attenuates inflammatory response and improves cognitive function in chronic ischemic stroke mice. Medicines (Basel). 3:E162016. View Article : Google Scholar : PubMed/NCBI
43	Chen Y, Zhang L, Yu H, Song K, Shi J, Chen L and Cheng J: Necrostatin-1 improves long-term functional recovery through protecting oligodendrocyte precursor cells after transient focal cerebral ischemia in mice. Neuroscience. 371:229–241. 2018. View Article : Google Scholar : PubMed/NCBI
44	Fan H, Tang HB, Kang J, Shan L, Song H, Zhu K, Wang J, Ju G and Wang YZ: Involvement of endoplasmic reticulum stress in the necroptosis of microglia/macrophages after spinal cord injury. Neuroscience. 311:362–373. 2015. View Article : Google Scholar : PubMed/NCBI