Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (5): 1-7.doi: 10.6040/j.issn.1671-7554.0.2022.0102

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Protective effect and mechanism of growth differentiation factor-15 in LPS-induced models of Parkinsons disease

ZHANG Xiufang, LI Peizheng, ZHANG Bohan, SUN Congcong, LIU Yiming   

  1. Department of Neurology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2022-06-01

Abstract: Objective To investigate the protective effect and mechanism of growth differentiation factor 15(GDF15)in lipopolysaccharide(LPS)induced neuroinflammation associated with Parkinsons disease. Methods To explore the optimum time of LPS, BV2 cells were divided into blank, 3 h, 6 h, 12 h and 24 h groups; to explore the optimum concentration of LPS, BV2 cells were divided into blank, 0.5, 1 and 2mg/mL groups; to explore the effect of GDF15, BV2 cells were divided into blank, LPS and LPS+GDF15 groups. The mice were divided into WT, WT+LPS and KO-LPS group. The protein expressions of STAT3, NF-κB and ERK were detected with Western blotting. The mRNA expressions of TNF-α, IL-1β, iNOS and COX-2 were detected with qPCR. The effect of GDF15 on the morphology of LPS-induced BV2 cells was observed with a microscope. Results GDF-15 suppressed the expressions of TNF-α, IL-1β, iNOS and COX-2 by inhibiting the STAT3/NF-κB/ERK signaling pathway. In the substantia nigra and striatum of the GDF15 knockout mice, the expressions of TNF-α, IL-1β, iNOS and COX-2 increased. Conclusion GDF15 can attenuate the expressions of TNF-α, IL-1β, iNOS and COX-2 through STAT3/NF-κB/ERK signaling pathway, indicating it is a protective factor in the progression of Parkinsons disease. It can provide a new therapeutic target for the prevention and treatment of this disease.

Key words: Growth differentiation factor 15, Parkinsons disease, Neuroinflammation, Signal pathway, Mice

CLC Number: 

  • R574
[1] Bloem BR, Okun MS, Klein C. Parkinsons disease [J]. Lancet, 2021, 397(10291): 2284-2303.
[2] Pajares M, Rojo AI, Manda G, et al. Inflammation in Parkinsons disease: mechanisms and therapeutic implications [J]. Cells, 2020, 9(7): 1687.
[3] Chrysoula M, Maria S, Efthimios D, et al. Neurodegeneration and inflammation-an interesting interplay in Parkinsons disease [J]. Int J Mol Sci, 2020, 21(22): 8421.
[4] McGeer PL, Itagaki S, Boyes BE, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinsons and Alzheimers disease brains [J]. Neurology, 1988, 38(8): 1285-1291.
[5] Ouchi Y, Yagi S, Yokokura M, et al. Neuroinflammation in the living brain of Parkinsons disease [J]. Park Relat Disord, 2009, 15(Suppl 3): 200-204.
[6] Nagatsu T, Mogi M, Ichinose H, et al. Cytokines in Parkinsons disease [J]. J Neural Transm Suppl, 2000(58): 143-151.
[7] Huang B, Liu J, Meng T, et al. Polydatin prevents lipopolysaccharide(LPS)-induced parkinsons disease via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis [J]. Front Immunol, 2018, 9: 2527. doi: 10.3389/fimmu.2018.02527.
[8] Lai JL, Liu YH, Liu C, et al. Indirubin inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways [J]. Inflammation, 2017, 40(1): 1-12.
[9] Corre J, Hébraud B, Bourin P. Concise review: growth differentiation factor 15 in pathology: a clinical role? [J]. Stem Cells Transl Med, 2013, 2(12): 946-952.
[10] Breit SN, Johnen H, Cook AD, et al. The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism [J]. Growth Factors, 2011, 29(5): 187-195.
[11] Unsicker K, Spittau B, Krieglstein K. The multiple facets of the TGF-β family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1 [J]. Cytokine Growth Factor Rev, 2013, 24(4): 373-384.
[12] Yao XM, Wang D, Zhang L, et al. Serum growth differentiation factor 15 in parkinson disease [J]. Neuro Degener Dis, 2017, 17(6): 251-260.
[13] Machado V, Haas SJ, von Bohlen Und Halbach O, et al. Growth/differentiation factor-15 deficiency compromises dopaminergic neuron survival and microglial response in the 6-hydroxydopamine mouse model of Parkinsons disease [J]. Neurobiol Dis, 2016, 88: 1-15. doi: 10.1016/j.nbd.2015.12.016.
[14] Machado V, Gilsbach R, Das R, et al. Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice [J]. Cell Tissue Res, 2016, 365(2): 209-223.
[15] Nam HY, Nam JH, Yoon G, et al. Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice [J]. J Neuroinflammation, 2018, 15(1): 271.
[16] Yang L, Zhou R, Tong Y, et al. Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation [J]. Neurobiol Dis, 2020, 140: 104814. doi: 10.1016/j.nbd.2020.104814.
[17] Wu SY, Pan BS, Tsai SF, et al. BDNF reverses aging-related microglial activation [J]. J Neuroinflammation, 2020, 17(1): 210.
[18] Zhang R, Rupa EJ, Zheng S, et al. Panos-fermented extract-mediated nanoemulsion: preparation, characterization, and in vitro anti-inflammatory effects on RAW 264.7 cells [J]. Molecules, 2021, 27(1): 218.
[19] McGeer PL, Itagaki S, Boyes BE, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinsons and Alzheimers disease brains [J]. Neurology, 1988, 38(8): 1285-1291.
[20] Jiang WW, Zhang ZZ, He PP, et al. Emerging roles of growth differentiation factor-15 in brain disorders(Review)[J]. Exp Ther Med, 2021, 22(5): 1270.
[21] Conte M, Martucci M, Chiariello A, et al. Mitochondria, immunosenescence and inflammaging: a role for mitokines? [J]. Semin Immunopathol, 2020, 42(5): 607-617.
[22] Gliozzi M, Scicchitano M, Bosco F, et al. Modulation of nitric oxide synthases by oxidized LDLs: role in vascular inflammation and atherosclerosis development [J]. Int J Mol Sci, 2019, 20(13): 3294-3294.
[23] Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3 [J]. Nat Rev Cancer, 2009, 9(11): 798-809.
[24] Samidurai M, Ramasamy VS, Jo J. Β-amyloid inhibits hippocampal LTP through TNFR/IKK/NF-κb pathway [J]. Neurol Res, 2018, 40(4): 268-276.
[25] Jones SV, Kounatidis I. Nuclear factor-kappa B and alzheimer disease, unifying genetic and environmental risk factors from cell to humans [J]. Front Immunol, 2017, 8: 1805. doi: 10.3389/fimmu.2017.01805.
[26] Sun Y, Liu WZ, Liu T, et al. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis [J]. J Recept Signal Transduct Res, 2015, 35(6): 600-604.
[27] Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases [J]. Microbiol Mol Biol Rev, 2011, 75(1): 50-83.
[28] Mogi M, Togari A, Kondo T, et al. Caspase activities and tumor necrosis factor receptor R1(p55)level are elevated in the substantia nigra from Parkinsonian brain [J]. J Neural Transm, 2000, 107(3): 335-341.
[29] Zhang Q, Lenardo MJ, Baltimore D. 30 years of NF-κB: a blossoming of relevance to human pathobiology [J]. Cell, 2017, 168(1/2): 37-57.
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