title: 6-Mer Hyaluronan Oligosaccharides Modulate Neuroinflammation and α-Synuclein Expression in Neuron-Like SH-SY5Y Cells.
abstract: Several studies have shown the degradation of the extracellular matrix at the site of neuroinflammation and increased release of degradation products of glycosaminoglycans. Among these, low molecular weight fragments of hyaluronan (HA) may play a key role in the events leading to neuroinflammation and/or neuronal degeneration. Small HA fragments are able to induce inflammation by stimulating both TLR-2 and TLR-4 as well as CD44 receptors. This stimulation culminates in the nuclear translocation of NF-kB that in turn induces the production of pro-inflammatory intermediates such as TNF-α and IL-1β. The potential of HA fragments, as mediators of inflammation, it has been poorly investigated in neuron-like SH-SY5Y cells so the aim of this study was to investigate the neuroinflammatory effects of very small HA oligosaccharides, the involvement of TLR-2, TLR-4, and CD44 and the production of α-synuclein in such cells. The addition of HA fragments to cell cultures up-regulated TLR-2, TLR-4, and CD44 levels, induced NF-kB activity and increased both TNF-α and IL-β as well as α-synuclein production. On blocking the activity of TLR-2, TLR-4, and CD44 the levels of inflammatory parameters and of α-synuclein were significantly reduced. Since several data have shown as α-synuclein, produced from neurons, is able to initiate ex novo or to maintain an existing neuroinflammatory response, which has been suggested as one of the principal components involved in neurodegenerative pathologies, as PD, we suggest that HA pathways should be given careful consideration when devising future anti-neuroinflammatory strategies to defend against the onset of neurodegenerative disorders. J. Cell. Biochem. 117: 2835-2843, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy. mscuruchi@unime.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Scuruchi
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Policlinico Universitario, 98125, Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Policlinico Universitario, 98125, Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Avenoso
authors.affiliation: Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Policlinico Universitario, 98125, Messina, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Campana
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy.
authors.forename: Yousef A
authors.initials: YA
authors.lastname: Abusamra
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Policlinico Universitario, 98125, Messina, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Calatroni
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy.
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Campo
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Policlinico Universitario, 98125, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009844:Oligosaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D009844:Oligosaccharides; D012333:RNA, Messenger; D051844:alpha-Synuclein; D006820:Hyaluronic Acid
keywords: CYTOKINES; HYALURONAN; INFLAMMATION; SH-SY5Y CELLS; TLRs; α-SYNUCLEIN