title: Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke.
abstract: Accumulating evidence shows that post-ischemic inflammation originated by Toll-like receptors (TLR) plays critical roles in ischemic stroke. However, the functions of other innate immune receptors are poorly understood in cerebral ischemia. Macrophage-inducible C-type lectin, Mincle, is one of the innate immune receptor C-type lectin-like receptor (CLR) to response against dying cells. In the present study, we showed that Mincle, its ligand SAP130, and its downstream phospho-Syk/Syk were upregulated after ischemia, and that Mincle is expressed in immune and non-immune cells in the ischemic brains of mice and human. We treated mice with piceatannol, a Syk inhibitor, and consequently the infarct volume and swelling were suppressed by piceatannol. The levels of phospho-Syk, MMP9 and ICAM-1 were downregulated, and the level of Claudin5 was uplegurated in piceatannol-treated groups. These data indicate that innate immune system, such as Mincle and Syk plays a pivotal role in the pathogenesis after the ischemia and reperfusion.
authors.affiliation: 1] Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501-1196, Japan [2] Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakano
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mishiro
authors.forename: Toshinori
authors.initials: T
authors.lastname: Takagi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007511:Ischemia / Q000276:immunology / Q000473:pathology* / Q000662:veterinary; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D020521:Stroke / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000072377:Syk Kinase; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C113583:Clecsf8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D020011:Protective Agents; D013267:Stilbenes; D018799:Intercellular Adhesion Molecule-1; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D020780:Matrix Metalloproteinase 9