Tumor necrosis factor α-converting enzyme inhibitor attenuates lipopolysaccharide

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Eun Hui Bae In Jin Kim Hong Sang Choi Ha Yeon Kim Chang Seong Kim Seong Kwon Ma In S. Kim Soo Wan Ki
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제22권 제2호, 135~143쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2018.03.31

영문 초록

Tumor necrosis factor-α (TNFα) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which TNFα-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS (10 μg/ml) in the presence or absence of a type 1 TACE inhibitor (1μM) or type 2 TACE inhibitor (10 μM). LPS treatment induced increased serum creatinine,TNFα, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore,inhibitors of TACE are potential therapeutic agents for kidney injury.

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키워드

Acute kidney injury Angiotensin-converting enzyme-2 Lipopolysaccharide Mitogen activated protein kinase Oxidative stress TNFα-converting enzyme