SpringerLink
Log in

Decreased SIRT1 mRNA expression in peripheral blood mononuclear cells from patients with neuromyelitis optica spectrum disorders

  • Original article
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

Objective

Sirtuin (SIRT)1, as a molecular link between immunity and metabolic pathways, is a key immune response regulator. The significance of SIRT1 in peripheral blood mononuclear cells (PBMCs) of neuromyelitis optica spectrum disorder (NMOSD) has not been investigated. Here, we aimed to evaluate the SIRT1 mRNA level in PBMCs of patients with NMOSD and its clinical relevance and explore the potential mechanism of SIRT1 action.

Methods

A total of 65 patients with NMOSD and 60 normal controls from North China were enrolled. Using real-time fluorescence quantitative-polymerase chain reaction, mRNA levels were detected in PBMCs, and protein levels were detected using western blotting.

Results

Compared to the healthy controls and chronic-phase patients with NMOSD, SIRT1 mRNA and protein levels in PBMCs of NMOSD patients with acute attack were significantly downregulated (p < 0.0001). ∆EDSS scores (EDSS scores in the acute phase—EDSS scores before the recent attack) were higher in NMOSD patients with low SIRT1 mRNA level than in patients with high SIRT1 expression (p = 0.042). SIRT1 mRNA level in patients with acute-phase NMSOD was positively correlated with lymphocyte and monocyte counts and negatively correlated with neutrophil counts and the neutrophil-to-lymphocyte ratio. Furthermore, the transcription factor FOXP3 mRNA level was significantly positively correlated with the SIRT1 mRNA level in PBMCs of patients with acute-phase NMOSD.

Conclusions

Our study indicated that SIRT1 mRNA expression was downregulated in the PBMCs of patients with acute-phase NMOSD, and its level was correlated with the clinical parameters of the patients, suggesting a potential role of SIRT1 in NMOSD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189

    Article  PubMed  PubMed Central  Google Scholar 

  2. Papp V, Magyari M, Aktas O et al (2021) Worldwide incidence and prevalence of neuromyelitis optica: a systematic review. Neurology 96:59–77

    PubMed  PubMed Central  Google Scholar 

  3. Wu X, Cao N, Fenech M, Wang X (2016) Role of sirtuins in maintenance of genomic stability: relevance to cancer and healthy aging. DNA Cell Biol 35:542–575

    Article  CAS  PubMed  Google Scholar 

  4. Chan SH, Hung CH, Shih JY et al (2017) SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease. Redox Biol 13:301–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kong S, McBurney MW, Fang D (2012) Sirtuin 1 in immune regulation and autoimmunity. Immunol Cell Biol 90:6–13

    Article  CAS  PubMed  Google Scholar 

  6. Lin QQ, Geng YW, Jiang ZW, Tian ZJ (2017) SIRT1 regulates lipopolysaccharide-induced CD40 expression in renal medullary collecting duct cells by suppressing the TLR4-NF-κB signaling pathway. Life Sci 170:100–107

    Article  CAS  PubMed  Google Scholar 

  7. Yu Q, Dong L, Li Y, Liu G (2018) SIRT1 and HIF1α signaling in metabolism and immune responses. Cancer Lett 418:20–26

    Article  CAS  PubMed  Google Scholar 

  8. Qiu Y, Zhou X, Liu Y, Tan S, Li Y (2021) The role of sirtuin-1 in immune response and systemic lupus erythematosus. Front Immunol 12:632383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu YJ, Fang WJ, Pan S et al (2021) Regulation of Sirt1 on energy metabolism and immune response in rheumatoid arthritis. Int Immunopharmacol 101:108175

    Article  CAS  PubMed  Google Scholar 

  10. Martin A, Tegla CA, Cudrici CD et al (2015) Role of SIRT1 in autoimmune demyelination and neurodegeneration. Immunol Res 61:187–197

    Article  CAS  PubMed  Google Scholar 

  11. Lopez JA, Denkova M, Ramanathan S, Dale RC, Brilot F (2021) Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. Clin Transl Immunology 10:e1316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hewes D, Tatomir A, Kruszewski AM et al (2017) SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis. Exp Mol Pathol 102:191–197

    Article  CAS  PubMed  Google Scholar 

  13. Li R, Sun X, Shu Y et al (2017) Serum CCL20 and its association with SIRT1 activity in multiple sclerosis patients. J Neuroimmunol 313:56–60

    Article  PubMed  Google Scholar 

  14. Nimmagadda VK, Makar TK, Chandrasekaran K et al (2017) SIRT1 and NAD+ precursors: therapeutic targets in multiple sclerosis a review. J Neuroimmunol 304:29–34

    Article  CAS  PubMed  Google Scholar 

  15. Nimmagadda VK, Bever CT, Vattikunta NR et al (2013) Overexpression of SIRT1 protein in neurons protects against experimental autoimmune encephalomyelitis through activation of multiple SIRT1 targets. J Immunol 190:4595–4607

    Article  CAS  PubMed  Google Scholar 

  16. Foolad F, Khodagholi F, Nabavi SM, Javan M (2020) Changes in mitochondrial function in patients with neuromyelitis optica; correlations with motor and cognitive disabilities. PLoS ONE 15:e0230691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wu Y, Zhong L, Geng J (2019) Neuromyelitis optica spectrum disorder: pathogenesis, treatment, and experimental models. Mult Scler Relat Disord 27:412–418

    Article  PubMed  Google Scholar 

  18. Wojkowska DW, Szpakowski P, Ksiazek-Winiarek D, Leszczynski M, Glabinski A (2014) Interactions between neutrophils, Th17 cells, and chemokines during the initiation of experimental model of multiple sclerosis. Mediators Inflamm 2014:590409

    Article  PubMed  PubMed Central  Google Scholar 

  19. Schroeder-Castagno M, Del Rio-Serrato A, Wilhelm A et al (2022) Impaired response of blood neutrophils to cell-death stimulus differentiates AQP4-IgG-seropositive NMOSD from MOGAD. J Neuroinflammation 19(1):239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kira J (2011) Neuromyelitis optica and opticospinal multiple sclerosis: mechanisms and pathogenesis. Pathophysiology 18:69–79

    Article  CAS  PubMed  Google Scholar 

  21. Gibson PH, Croal BL, Cuthbertson BH et al (2007) Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J 154:995–1002

    Article  CAS  PubMed  Google Scholar 

  22. Núñez J, Núñez E, Bodí V et al (2008) Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol 101:747–752

    Article  PubMed  Google Scholar 

  23. Rifaioglu EN, BülbülŞen B, Ekiz Ö, CigdemDogramaci A (2014) Neutrophil to lymphocyte ratio in Behçet’s disease as a marker of disease activity. Acta Dermatovenerol Alp Pannonica Adriat 23:65–67

    PubMed  Google Scholar 

  24. Demirci S, Demirci S, Kutluhan S, Koyuncuoglu HR, Yurekli VA (2016) The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis. Int J Neurosci 126:700–706

    CAS  PubMed  Google Scholar 

  25. Qin B, Ma N, Tang Q et al (2016) Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol 26:372–376

    Article  PubMed  Google Scholar 

  26. CarneroContentti E, Delgado-García G, Criniti J et al (2021) An abnormally high neutrophil-to-lymphocyte ratio Is not an independent outcome predictor in AQP4-IgG-Positive NMOSD. Front Immunol 12:628024

    Article  Google Scholar 

  27. **e H, Zhao Y, Pan C et al (2021) Association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of first attack neuromyelitis optica spectrum disorder (NMOSD): a retrospective cohort study. BMC Neurol 21:389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chen X, Lu Y, Zhang Z, Wang J, Yang H, Liu G (2015) Intercellular interplay between Sirt1 signalling and cell metabolism in immune cell biology. Immunology 145:455–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang Y, Li Y, Li J et al (2019) SIRT1 alleviates isoniazid-induced hepatocyte injury by reducing histone acetylation in the IL-6 promoter region. Int Immunopharmacol 67:348–355

    Article  CAS  PubMed  Google Scholar 

  30. Hofer LS, Ramberger M, Gredler V et al (2020) Comparative Analysis of T-cell responses to aquaporin-4 and Myelin oligodendrocyte glycoprotein in Inflammatory demyelinating central nervous system diseases. Front Immunol 11:1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Limagne E, Thibaudin M, Euvrard R et al (2017) Sirtuin-1 activation controls tumor growth by impeding Th17 differentiation via STAT3 deacetylation. Cell Rep 19:746–759

    Article  CAS  PubMed  Google Scholar 

  32. Ma F, Hao H, Gao X et al (2020) Melatonin ameliorates necrotizing enterocolitis by preventing Th17/Treg imbalance through activation of the AMPK/SIRT1 pathway. Theranostics 10:7730–7746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kwon HS, Lim HW, Wu J, Schnölzer M, Verdin E, Ott M (2012) Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells. J Immunol 188:2712–2721

    Article  CAS  PubMed  Google Scholar 

  34. Lim HW, Kang SG, Ryu JK et al (2015) SIRT1 deacetylates RORγt and enhances Th17 cell generation. J Exp Med 212:607–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jamebozorgi K, Rostami D, Pormasoumi H, Taghizadeh E, Barreto GE, Sahebkar A (2021) Epigenetic aspects of multiple sclerosis and future therapeutic options. Int J Neurosci 131:56–64

    Article  PubMed  Google Scholar 

  36. Pedre X, Mastronardi F, Bruck W, López-Rodas G, Kuhlmann T, Casaccia P (2011) Changed histone acetylation patterns in normal-appearing white matter and early multiple sclerosis lesions. J Neurosci 31:3435–3445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yang Y, Tang Q, Zhao M et al (2015) The effect of mycophenolic acid on epigenetic modifications in lupus CD4+T cells. Clin Immunol 158:67–76

    Article  CAS  PubMed  Google Scholar 

  38. Wang Z, Long H, Chang C, Zhao M, Lu Q (2018) Crosstalk between metabolism and epigenetic modifications in autoimmune diseases: a comprehensive overview. Cell Mol Life Sci 75:3353–3369

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Natural Science Foundation of Hebei Province (H202206483).

Author information

Authors and Affiliations

  1. Department of Neurology, The Second Hospital of Hebei Medical University, No. 215, He**xi Road, Shijiazhuang, 050000, China

    Lu Zhang, Yumei Xue, Congcong Yuan, **aochen Du, Xuan Wang, Li Guo & Bin Li

  2. Key Laboratory of Neurology of Hebei Province, Shijiazhuang, China

    Lu Zhang, Yumei Xue, Congcong Yuan, **aochen Du, Xuan Wang, Li Guo & Bin Li

  3. Department of Pharmacy, Shijiazhuang People’s Hospital, Shijiazhuang, China

    Yumei Xue

  4. Department of Neurology, Baoding First Central Hospital, Baoding, China

    Congcong Yuan

Authors
  1. Lu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yumei Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Congcong Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. **aochen Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. LG, BL, and LZ conceived the study. Material preparation, data collection, and analysis were performed by LZ, YX, CY, and XD. XW was responsible for data management. LZ prepared the draft version of the manuscript, and all authors contributed to the manuscript. LG and BL are the guarantors of the content of the manuscript, including the data and analysis.

Corresponding authors

Correspondence to Li Guo or Bin Li.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of The Second Hospital of Hebei Medical University (Shijiazhuang, Hebei, China).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, L., Xue, Y., Yuan, C. et al. Decreased SIRT1 mRNA expression in peripheral blood mononuclear cells from patients with neuromyelitis optica spectrum disorders. Acta Neurol Belg 123, 2287–2294 (2023). https://doi.org/10.1007/s13760-023-02300-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-023-02300-3

Keywords

Search

Navigation