Curcumin modulates SDF-1alpha/CXCR4-induced migration of human retinal endothelial cells (HRECs)

Zaheer Sameermahmood, Muthuswamy Balasubramanyam, Thangavel Saravanan, Mohan Rema
Investigative Ophthalmology & Visual Science 2008, 49 (8): 3305-11

PURPOSE: The stromal-derived factor (SDF)-1alpha and the CXC receptor (CXCR)-4 jointly regulate the trafficking of various cell types and play a pivotal role in cell migration, proliferation, and survival. The purpose of this study was to assess whether curcumin inhibits human retinal endothelial cell (HREC) migration by interfering with SDF-1alpha/CXCR4 signaling.

METHODS: Primary HREC culture was established and maintained in endothelial growth medium. The viability and proliferation of HRECs were assessed by MTT and thymidine uptake assays, respectively. The effect of SDF-1alpha-induced HREC migration (chemotaxis) in the presence and absence of curcumin was determined using the Boyden chamber migration assay. Intracellular Ca(2+) concentration was measured by fluorometric analysis. Immunofluorescence and Western blot analyses were performed to quantify CXCR4, phosphorylated AKT, and PI3-kinase expression levels.

RESULTS: HREC migration increased in a dose-dependent manner (1, 10, 50, and 100 ng/mL; P < 0.001) in SDF-1alpha-treated cells. In contrast, AMD3100, an inhibitor of CXCR4 effectively inhibited HREC migration dose dependently. HREC migration was decreased when the cells were exposed to EGTA, a chelator of Ca(2+). Curcumin also blocked Ca(2+) influx, an important signal for HREC migration. In addition, curcumin significantly (P < 0.001) decreased SDF-1alpha-induced HRECs migration and downregulated SDF-1alpha-induced expression of CXCR4, phospho-AKT, phospho-phosphatidylinositol-3-kinase (PI3-K), and eNOS.

CONCLUSIONS: This study indicates that curcumin has an inhibitory effect on SDF-1alpha-induced HREC migration. The plausible mechanism of action could be upstream blockage of Ca(2+) influx and the downstream reduction of PI3-K/AKT signals.

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