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Reduction of Inflammatory Response in the Mouse Brain With Adenoviral-Mediated Transforming Growth Factor-β1 Expression

2001; Lippincott Williams & Wilkins; Volume: 32; Issue: 2 Linguagem: Inglês

10.1161/01.str.32.2.544

1524-4628

Li Pang, Wen Ye, Xiao-Ming Che, Blake J. Roessler, A. Lorris Betz, Guo-Yuan Yang,

Neuroinflammation and Neurodegeneration Mechanisms

Background and Purpose —Chemokines have been shown to play an important role in leukocyte and monocyte/macrophage infiltration into ischemic regions. The purpose of this study is to identify whether overexpression of the active human transforming growth factor-β1 (ahTGF-β1) can downregulate expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and intercellular adhesion molecule-1 (ICAM-1) and reduce ischemic brain injury. Methods —Overexpression of transforming growth factor-β1 (TGF-β1) was achieved through adenoviral gene transfer. Five days after adenoviral transduction, the mouse underwent 30 minutes of middle cerebral artery occlusion followed by 1 to 7 days of reperfusion. TGF-β1, MCP-1, MIP-1α, and ICAM-1 were detected by enzyme-linked immunosorbent assay and immunohistochemistry. Infarct areas and volumes were measured by cresyl violet staining. Results —MCP-1 and MIP-1α expression is increased after middle cerebral artery occlusion, and double-labeled immunostaining revealed that MCP-1 is colocalized with neurons and astrocytes. Viral-mediated TGF-β1 overexpression was significantly greater at measured time points, with a peak at 7 to 9 days. The expression of MCP-1 and MIP-1α, but not ICAM-1, was reduced in the mice overexpressing ahTGF-β1 ( P <0.05). Furthermore, infarct volume was significantly reduced in the mice overexpressing ahTGF-β1 ( P <0.05). Conclusions —This study demonstrates that MCP-1 and MIP-1α expressed in the ischemic region may play an important role in attracting inflammatory cells. The reduction of MCP-1 and MIP-1α, but not ICAM-1, in the mice overexpressing ahTGF-β1 suggests that the neuroprotective effect of TGF-β1 may result from the inhibition of chemokines during cerebral ischemia and reperfusion.