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

Suzuki Y, Nakano Y, Mishiro K, Takagi T, Tsuruma K, Nakamura M, Yoshimura S, Shimazawa M, Hara H - Sci Rep (2013)

Bottom Line: Macrophage-inducible C-type lectin, Mincle, is one of the innate immune receptor C-type lectin-like receptor (CLR) to response against dying cells.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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

The time-course of changes in protein levels of Mincle, SAP130, p-Syk, and Syk after reperfusion following 2 h of focal ischemia in mice.Quantitative analysis with western blot shows that the expression levels of (A) Mincle, (B) SAP130, (C) p-Syk, and (D) Syk were significantly increased at 2 h after ischemia and at 4 h, 10 h, and 22 h after reperfusion, but not at 3 days. Cropped blots are used in the figure. These gels were run under same experimental condition. * P < 0.05, ** P < 0.01 vs. control, n = 8.
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f2: The time-course of changes in protein levels of Mincle, SAP130, p-Syk, and Syk after reperfusion following 2 h of focal ischemia in mice.Quantitative analysis with western blot shows that the expression levels of (A) Mincle, (B) SAP130, (C) p-Syk, and (D) Syk were significantly increased at 2 h after ischemia and at 4 h, 10 h, and 22 h after reperfusion, but not at 3 days. Cropped blots are used in the figure. These gels were run under same experimental condition. * P < 0.05, ** P < 0.01 vs. control, n = 8.

Mentions: We tested changes in the protein levels of Mincle, SAP130, p-Syk, and Syk in brain tissue by western blot at 2 h after ischemia and at 4 h, 10 h, 22 h, and 3 days after reperfusion. All 4 proteins were significantly increased at 2 h after ischemia and at 4 h, 10 h, and 22 h after reperfusion, but not at 3 days post-reperfusion (Fig 2A to D). The trends of Mincle and SAP130 were similar, with expression levels peaking at 2 h after ischemia and gradually reducing up to 22 h after reperfusion (Fig 2A to B). On the other hand, p-Syk and Syk were increased at 2 h after ischemia and were sustained at the same level to 22 h after reperfusion (Fig 2C to D).


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

Suzuki Y, Nakano Y, Mishiro K, Takagi T, Tsuruma K, Nakamura M, Yoshimura S, Shimazawa M, Hara H - Sci Rep (2013)

The time-course of changes in protein levels of Mincle, SAP130, p-Syk, and Syk after reperfusion following 2 h of focal ischemia in mice.Quantitative analysis with western blot shows that the expression levels of (A) Mincle, (B) SAP130, (C) p-Syk, and (D) Syk were significantly increased at 2 h after ischemia and at 4 h, 10 h, and 22 h after reperfusion, but not at 3 days. Cropped blots are used in the figure. These gels were run under same experimental condition. * P < 0.05, ** P < 0.01 vs. control, n = 8.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3822396&req=5

f2: The time-course of changes in protein levels of Mincle, SAP130, p-Syk, and Syk after reperfusion following 2 h of focal ischemia in mice.Quantitative analysis with western blot shows that the expression levels of (A) Mincle, (B) SAP130, (C) p-Syk, and (D) Syk were significantly increased at 2 h after ischemia and at 4 h, 10 h, and 22 h after reperfusion, but not at 3 days. Cropped blots are used in the figure. These gels were run under same experimental condition. * P < 0.05, ** P < 0.01 vs. control, n = 8.
Mentions: We tested changes in the protein levels of Mincle, SAP130, p-Syk, and Syk in brain tissue by western blot at 2 h after ischemia and at 4 h, 10 h, 22 h, and 3 days after reperfusion. All 4 proteins were significantly increased at 2 h after ischemia and at 4 h, 10 h, and 22 h after reperfusion, but not at 3 days post-reperfusion (Fig 2A to D). The trends of Mincle and SAP130 were similar, with expression levels peaking at 2 h after ischemia and gradually reducing up to 22 h after reperfusion (Fig 2A to B). On the other hand, p-Syk and Syk were increased at 2 h after ischemia and were sustained at the same level to 22 h after reperfusion (Fig 2C to D).

Bottom Line: Macrophage-inducible C-type lectin, Mincle, is one of the innate immune receptor C-type lectin-like receptor (CLR) to response against dying cells.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus