Home » Key Scientific Articles » Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells

Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells

Sutinen EM1, Korolainen MA2, Häyrinen J3, Alafuzoff I4, Petratos S5, Salminen A6, Soininen H7, Pirttilä T7, Ojala JO1.

Front Cell Neurosci. 2014;8:214.

Show Affiliations

1Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland Kuopio, Finland ; Brain Research Unit, Clinical Research Centre, University of Eastern Finland Kuopio, Finland.

2Institute of Biotechnology, University of Helsinki Helsinki, Finland.and

3School of Medicine, Institute of Biomedicine, University of Eastern Finland Kuopio, Finland.

4Rudbecklaboratoriet, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology, Uppsala University Uppsala, Sweden.

5Regenerative Neuroscience and Development Laboratory, Department of Medicine, Central Clinical School, Monash University Prahran, VIC, Australia.

6Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland Kuopio, Finland ; Department of Neurology, Kuopio University Hospital Kuopio, Finland.

7Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland Kuopio, Finland ; Brain Research Unit, Clinical Research Centre, University of Eastern Finland Kuopio, Finland ; Department of Neurology, Kuopio University Hospital Kuopio, Finland.

 

Abstract

Chronic inflammation and oxidative stress (OS) are present in Alzheimer’s disease (AD) brains in addition to neuronal loss, Amyloid-{Beta} (A{Beta}) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18, are elevated in post-mortem AD brains. Interleukin-18 can modulate the tau kinases, Cdk5 and GSK3{Beta}, as well as A{Beta}-production. Interleukin-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other interleukin-18 regulated proteins in neuron-like SH-SY5Ycells. Differentiated SH-SY5Y cells, incubated with interleukin-18 for 24, 48, or 72 h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE). Specific altered protein spots were chosen and identified with mass spectrometry (MS) and verified by western immunoblotting (WIB). Interleukin-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous  protein levels/modifications. We concentrated on those related to OS (DDAH2, peroxiredoxins 2, 3, and 6, DJ-1, BLVRA), A{Beta}-degradation (MMP14, TIMP2), A{Beta}-aggregation (Septin-2), and modifications of axon growth and guidance associated, collapsin response mediator protein 2 (CRMP2). IL-18 significantly increased antioxidative enzymes, indicative of OS, and altered levels of glycolytic {Alpha}- and {Gamma}-enolase and multifunctional 14-3-3{Gamma} and -ε, commonly affected in neurodegenerative diseases. MMP14, TIMP2, {Alpha}-enolase and 14-3-3ε, indirectly involved in A{Beta} metabolism, as well as Septin-2 showed changes that increase A{Beta} levels. Increased 14-3-3{Gamma} may contribute to GSK3{Beta} driven tau hyperphosphorylation and CRMP2 Thr514 and Ser522 phosphorylation with the Thr555-site, a target for Rho kinase, showing time-dependent changes. Interleukin-18also increased caspase-1 levels and vacuolization of the cells. Although our SH-SY5Y cells were not aged, as neurons in AD, our work suggests that heightened or prolonged Interleukin-18 levels can drive protein changes of known relevance to AD pathogenesis.

Go To PubMed

Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells. Global Medical Discovery