Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke

Yukiya Suzuki; Yusuke Nakano; Keisuke Mishiro; Toshinori Takagi; Kazuhiro Tsuruma; Mitsuhiro Nakamura; Shinichi Yoshimura; Masamitsu Shimazawa; Hideaki Hara

doi:10.1038/srep03177

Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke

Sci Rep. 2013 Nov 11:3:3177. doi: 10.1038/srep03177.

Authors

Yukiya Suzuki¹, Yusuke Nakano, Keisuke Mishiro, Toshinori Takagi, Kazuhiro Tsuruma, Mitsuhiro Nakamura, Shinichi Yoshimura, Masamitsu Shimazawa, Hideaki Hara

Affiliation

¹ 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.

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.

MeSH terms

Animals
Brain / drug effects
Brain / metabolism
Brain / pathology
Down-Regulation / drug effects
Humans
Immunity, Innate*
In Vitro Techniques
Intercellular Adhesion Molecule-1 / metabolism
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / metabolism*
Ischemia / immunology
Ischemia / pathology*
Ischemia / veterinary
Lectins, C-Type / metabolism*
Male
Matrix Metalloproteinase 9 / metabolism
Membrane Proteins / metabolism*
Mice
Protective Agents / chemistry
Protective Agents / pharmacology
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / metabolism*
Stilbenes / chemistry
Stilbenes / pharmacology
Stroke / immunology
Stroke / metabolism
Stroke / pathology
Syk Kinase
Up-Regulation / drug effects

Substances

Clecsf8 protein, mouse
Intracellular Signaling Peptides and Proteins
Lectins, C-Type
Membrane Proteins
Protective Agents
Stilbenes
Intercellular Adhesion Molecule-1
3,3',4,5'-tetrahydroxystilbene
Protein-Tyrosine Kinases
SYK protein, human
Syk Kinase
Syk protein, mouse
Matrix Metalloproteinase 9