Affiliation:
1. Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
Abstract
Status epilepticus (SE) evokes leukocyte infiltration in the frontoparietal cortex (FPC) without the blood-brain barrier disruption. Monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) regulate leukocyte recruitments into the brain parenchyma. Epigallocatechin-3-gallate (EGCG) is an antioxidant and a ligand for non-integrin 67-kDa laminin receptor (67LR). However, it is unknown whether EGCG and/or 67LR affect SE-induced leukocyte infiltrations in the FPC. In the present study, SE infiltrated myeloperoxidase (MPO)-positive neutrophils, as well as cluster of differentiation 68 (CD68)-positive monocytes in the FPC are investigated. Following SE, MCP-1 was upregulated in microglia, which was abrogated by EGCG treatment. The C–C motif chemokine receptor 2 (CCR2, MCP-1 receptor) and MIP-2 expressions were increased in astrocytes, which were attenuated by MCP-1 neutralization and EGCG treatment. SE reduced 67LR expression in astrocytes, but not endothelial cells. Under physiological conditions, 67LR neutralization did not lead to MCP-1 induction in microglia. However, it induced MIP-2 expression and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in astrocytes and leukocyte infiltration in the FPC. Co-treatment of EGCG or U0126 (an ERK1/2 inhibitor) attenuated these events induced by 67LR neutralization. These findings indicate that the EGCG may ameliorate leukocyte infiltration in the FPC by inhibiting microglial MCP-1 induction independent of 67LR, as well as 67LR-ERK1/2-MIP-2 signaling pathway in astrocytes.
Funder
National Research Foundation of Korea
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology
Cited by
1 articles.
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