Klotho Ameliorates Cellular Inflammation via Suppression of Cytokine Release and Upregulation of miR-29a in the PBMCs of Diagnosed Alzheimer’s Disease Patients

  • Mohsen SedighiEmail author
  • Tourandokht Baluchnejadmojarad
  • Soudabeh Fallah
  • Nariman Moradi
  • Siamak Afshin-Majdd
  • Mehrdad Roghani


Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by neural inflammation and oxidative stress. In the current study, the protective effects of klotho and linagliptin treatment on human peripheral blood mononuclear cells (PBMCs) of AD patients and healthy controls (HCs) are assessed through measurement of inflammatory cytokines, signaling proteins, and miRNA expression. Sixteen diagnosed AD patients and sixteen HCs were enrolled in the study. Blood samples were obtained and PBMCs were isolated. PBMCs were treated with klotho at different concentrations (0.5, 1, and 2 nM) and linagliptin (50 μM). The concentration of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), epsilon isoform of protein kinase C (PKCε), phosphorylated cyclic AMP response element binding (pCREB), and Wnt1 were measured by ELISA. The expression of miR-29a and miR-195 was detected by real-time PCR. The results showed that klotho significantly reduced IL-1β, IL-6, and TNF-α levels in both groups of the experiment. Linagliptin also remarkably reduced TNF-α levels in the AD group. Moreover, klotho caused the downregulation of Wnt1 in the PBMCs of both groups and the upregulation of the pCREB in HCs. Meanwhile, klotho induced miR-29a expression in the PBMCs of HCs, while miR-29a expression was induced in the AD group by klotho and linagliptin. The current findings revealed that klotho alleviates inflammation in human PBMCs, probably through the suppression of inflammatory cytokines and the upregulation of miR-29a, and part of its beneficial effect is mediated through appropriate modulation of the Wnt1/pCREB signaling cascade. In addition, linagliptin exerts protective effects by reducing TNF-α and inducing miR-29a expression in PBMCs.


Alzheimer’s disease Cytokines Klotho Linagliptin miRNAs 



This study has been adapted from a PhD thesis at Iran University of Medical Sciences (Tehran, Iran).


This work was financially supported (grant # 95-01-87-27994) by Iran University of Medical Sciences.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there is no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Iran University of Medical Sciences and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neuroscience, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran
  2. 2.Department of Physiology, School of MedicineIran University of Medical SciencesTehranIran
  3. 3.Department of Biochemistry, School of MedicineIran University of Medical SciencesTehranIran
  4. 4.Department of Clinical Biochemistry, Faculty of MedicineKurdistan University of Medical SciencesSanandajIran
  5. 5.Neurophysiology Research CenterShahed UniversityTehranIran
  6. 6.Department of NeurologySchool of Medicine, Shahed UniversityTehranIran

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