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

Yukiya Suzuki1, Yusuke Nakano, Keisuke Mishiro

  • 11] 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.

Scientific Reports
|November 12, 2013
PubMed

Insights

Post-ischemic inflammation involves Mincle, a C-type lectin-like receptor, and Syk signaling in ischemic stroke. Inhibiting Syk with piceatannol reduced stroke damage, highlighting Mincle-Syk as a therapeutic target.

Area of Science:

  • Immunology
  • Neuroscience
  • Pathology

Background:

  • Post-ischemic inflammation is crucial in ischemic stroke, with Toll-like receptors (TLRs) implicated.
  • The role of other innate immune receptors, like Mincle (Macrophage-inducible C-type lectin), in cerebral ischemia remains unclear.

Purpose of the Study:

  • To investigate the role of Mincle and its signaling pathway in the pathogenesis of ischemic stroke.
  • To evaluate the therapeutic potential of inhibiting the Mincle-Syk pathway.

Main Methods:

  • Upregulation of Mincle, SAP130, and phospho-Syk/Syk was assessed post-ischemia in mice and human brain samples.
  • Mice were treated with piceatannol, a Syk inhibitor, to evaluate its effects on infarct volume, swelling, and molecular markers.
  • Levels of phospho-Syk, MMP9, ICAM-1, and Claudin5 were analyzed in treated and control groups.

Main Results:

  • Mincle, SAP130, and phospho-Syk/Syk were upregulated following ischemia.
  • Mincle expression was observed in both immune and non-immune cells in ischemic brain tissue.
  • Piceatannol treatment significantly reduced infarct volume and brain swelling.
  • Downregulation of phospho-Syk, MMP9, and ICAM-1, and upregulation of Claudin5 were observed in the piceatannol-treated group.

Conclusions:

  • The Mincle-Syk signaling pathway is activated in ischemic stroke and contributes to pathogenesis.
  • Inhibition of Syk offers a potential therapeutic strategy for mitigating ischemic stroke injury.
  • These findings underscore the critical role of the innate immune system in post-ischemia reperfusion injury.

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