αシヌクレイン凝集体による脳ペリサイトの炎症性メディエーター産生におけるP糖タンパク質の関与

• Published in: 日本薬理学会年会要旨集 p. 3-P-197
• Main Authors: 松本, 純一, 横谷, みき, 高田, 芙友子, 有留, 尚孝, 小林, 篤史, 安永, 美保, 佐野, 和憲, 秋月, 美波, 岩尾, 卓朗, 道具, 伸也
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: blood-brain barrier; cytokine; transporter; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-197

The pathological hallmark of Parkinson disease (PD) is a widespread distribution of the aggregated α-synuclein (α-Syn) proteins in the inclusions known as Lewy bodies. Exogenous α-Syn secreted from neurons could induce neuroinflammation. We previously reported that pericytes, an essential component of the blood-brain barrier (BBB), released various inflammatory mediators in response to monomeric α-Syn through Toll-like receptor (TLR) 4. Here, we investigated whether α-Syn aggregates also induced the release of inflammatory mediators from pericytes. Then, we intended to characterize the α-Syn-activated pericytes. In response to α-Syn aggregates, pericytes released higher levels of IL-1β, IL-6, MCP-1, TNF-α and MMP-9 than the other cell types of the BBB (brain endothelial cells and astrocytes). TAK242 (a TLR4 inhibitor, 5 μM) inhibited the release of these mediators induced by a 24-hr exposure of α-Syn aggregates (5 μg/mL). P-glycoprotein (P-gp) expression in pericytes was increased by α-Syn aggregates concurrently with the release of inflammatory mediators. TAK242 also inhibited the α-Syn aggregate-induced increase in P-gp expression in pericytes. These results suggest that the increased P-gp expression in pericytes may characterize the α-Syn-activated pericytes and is involved in the release of inflammatory mediators from pericytes.