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Open AccessArticle

Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow, Werynia 2, 36-100 Kolbuszowa, Poland
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Cells 2020, 9(5), 1231; https://doi.org/10.3390/cells9051231
Received: 14 April 2020 / Revised: 7 May 2020 / Accepted: 15 May 2020 / Published: 16 May 2020
(This article belongs to the Section Cells of the Nervous System)
Neuroinflammation is defined as the activation of the brain’s innate immune system in response to an inflammatory challenge and is considered to be a prominent feature of neurodegenerative diseases. The contribution of overactivated neuroglial cells to neuroinflammation and neurodegenerative disorders is well documented, however, the role of hippocampal neurons in the neuroinflammatory process remains fragmentary. In this study, we show for the first time, that klotho acts as a signal transducer between pro-survival and pro-apoptotic crosstalk mediated by ER stress in HT-22 hippocampal neuronal cells during LPS challenge. In control HT-22 cells, LPS treatment results in activation of the IRE1α-p38 MAPK pathway leading to increased secretion of anti-inflammatory IL-10, and thus, providing adaptation mechanism. On the other hand, in klotho-deficient HT-22 cells, LPS induces oxi-nitrosative stress and genomic instability associated with telomere dysfunctions leading to p53/p21-mediated cell cycle arrest and, in consequence, to ER stress, inflammation as well as of apoptotic cell death. Therefore, these results indicate that klotho serves as a part of the cellular defense mechanism engaged in the protection of neuronal cells against LPS-mediated neuroinflammation, emerging issues linked with neurodegenerative disorders. View Full-Text
Keywords: klotho; lipopolysaccharide; HT-22 hippocampal neuronal cells; neuroinflammation; ER stress klotho; lipopolysaccharide; HT-22 hippocampal neuronal cells; neuroinflammation; ER stress
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Rusinek, K.; Sołek, P.; Tabęcka-Łonczyńska, A.; Koziorowski, M.; Mytych, J. Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation. Cells 2020, 9, 1231.

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