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Published on: January 4, 2018
Caffeic acid inhibits acute hyperhomocysteinemia-induced leukocyte rolling and adhesion in mouse cerebral venules
Hai-Ping Zhao1, Juan Feng, Kai Sun
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
Insights
Curcumin (CA) effectively reduces leukocyte rolling and adhesion in the brain during hyperhomocysteinemia (HHcy). This action is linked to decreased inflammation and suppressed signaling pathways in leukocytes.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Hyperhomocysteinemia (HHcy) is associated with increased leukocyte adhesion in cerebral venules, contributing to neuroinflammation.
- Leukocyte adhesion plays a critical role in the pathogenesis of cerebrovascular diseases.
Purpose of the Study:
- To investigate the therapeutic effects of curcumin (CA) on HHcy-induced leukocyte rolling and adhesion in mouse cerebral venules.
- To elucidate the underlying mechanisms of CA's action, including its impact on inflammatory mediators and signaling pathways.
Main Methods:
- Intravital microscopy was used to assess leukocyte rolling and adhesion in mouse cerebral venules following DL-homocysteine (DL-Hcy) and CA administration.
- Flow cytometry and immunohistochemistry were employed to evaluate reactive oxygen species (ROS) production, adhesion molecule expression, and signaling pathway activation (Src/PI3K/Akt).
Main Results:
- CA significantly inhibited HHcy-induced leukocyte rolling and adhesion in cerebral venules.
- CA reduced ROS production, pro-inflammatory cytokines (KC, MIP-2, MCP-1), and the expression of adhesion molecules (E-selectin, ICAM-1) on endothelium and leukocytes.
- CA suppressed CD18 phosphorylation and the Src/PI3K/Akt signaling pathway in leukocytes.
Conclusions:
- Curcumin demonstrates a protective effect against HHcy-induced leukocyte adhesion in cerebral venules.
- The anti-adhesive effects of CA are mediated by the downregulation of adhesion molecule expression and the suppression of the Src/PI3K/Akt pathway in leukocytes.
Objective:
To investigate the effects and possible mechanisms of CA on acute HHcy-induced leukocyte rolling and adhesion in mouse cerebral venules.
Methods:
Male C57 BL/6J mice were injected with DL-Hcy (50 mg/kg) and CA (10 mg/kg). The effect of CA on HHcy-induced leukocyte rolling and adhesion in cerebral vessels was assessed using intravital microscopy. Plasma cytokines and chemokines were evaluated by cytometric bead array. ROS production in HUVECs and adhesion molecule expression on leukocytes were determined by flow cytometry. E-selectin and ICAM-1 expression in cerebrovascular endothelium was detected by immunohistochemistry. CD18 phosphorylation and the Src/PI3K/Akt pathway in leukocytes were determined by confocal microscopy and Western blot.
Results:
CA inhibited HHcy-elicited leukocyte rolling and adhesion, decreased ROS production in HUVECs, and reduced plasma KC, MIP-2, and MCP-1 levels. CA reduced the E-selectin and ICAM-1 expression on cerebrovascular endothelium and CD11b/CD18 on leukocytes caused by HHcy. Of notice, CA depressed CD18 phosphorylation and the Src/PI3K/Akt pathway in leukocytes.
Conclusions:
CA inhibited HHcy-provoked leukocyte rolling and adhesion in cerebral venules, ameliorating adhesion molecule expression and activation, which is related to the suppression of the Src/PI3K/Akt pathway in leukocytes.
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